pHi监测在急性重症胰腺炎患者中的应用及意义

目的 :探讨胃粘膜内pH值 (pHi)监测在急性重症胰腺炎患者中的应用及其临床意义。方法 :对在临床观察期间收住院的 40例急性重症胰腺炎患者在入院后立刻经鼻插入TRIP -NGS导管并测定pHi,以后每隔 12h测量一次pHi。结果 :并发器官功能衰竭的急性重症胰腺炎患者在器官功能衰竭前 1～ 3dpHi即有显著降低 ,而同期测得的全身氧供指标并未发生明显异常。结论 :在急性重症胰腺炎患者中进行pHi监测具有操作简便、结果可靠等优点 ,对于早期发现局部组织缺氧、尽快采取措施预防器官功能衰竭的发生具有重要临床指导意义。     

急性重症胰腺炎时监测胃粘膜下pH值的临床意义

探讨在急性重症胰腺炎时通过动态监测胃粘膜下ＰＨ值,从而早期发现局部组织器官缺氧情况,及时采取措施预防器官功能衰竭的发生。方法对在临床观察期间收住院的４０例急性重症胰腺炎患者在入院后立刻经鼻插入ＴＲＩＰ－ＮＧＳ导管并测定Ｐｈｉ,以后每隔１２小时测量一次Ｐｈｉ。结果并发器官功能衰竭的急性重症胰腺炎患者在器官功能衰竭前１－３天Ｐｈ８即有显著降低,而同期测得的全身氧供指标并未发生明显。结论Ｐｈｉ具有操作简     

Acute pancreatitis: models, markers, and mediators

Acute pancreatitis has an incidence of approximately 40 cases per year per 100,000 adults. Although usually self-limiting, 10% to 20% of afflicted patients will progress to severe pancreatitis. The mortality rate among patients with severe pancreatitis may approach 30% when they progress to multisystem organ failure. The development of acute pancreatitis illustrates the requirement for understanding the basic mechanisms of disease progression to drive the exploration of therapeutic options. The pathogenesis of acute pancreatitis involves the interplay of local and systemic immune responses that are often difficult to characterize, particularly when results from animal models are used as a foundation for human trials. Experimental studies suggest that the prognosis for acute pancreatitis depends upon the degree of pancreatic necrosis and the intensity of multisystem organ failure generated by the systemic inflammatory response. This suggests an intricate balance between localized tissue damage with proinflammatory cytokine production and a systemic, anti-inflammatory response that restricts the inappropriate movement of proinflammatory agents into the circulation. The critical players of this interaction include the proinflammatory cytokines IL-1beta, TNF-alpha, IL-6, IL-8, and platelet activating factor (PAF). The anti-inflammatory cytokines IL-10, as well as TNF-soluble receptors and IL-1 receptor antagonist, have also been shown to be intimately involved in the inflammatory response to acute pancreatitis. Other compounds implicated in disease pathogenesis in experimental models include complement, bradykinin, nitric oxide, reactive oxygen intermediates, substance P, and higher polyamines. Several of these mediators have been documented to be present at increased concentrations in the plasma of patients with severe, acute pancreatitis. Preclinical work has shown that some of these mediators are markers for disease activity, whereas other inflammatory components may actually drive the disease process as important mediators. Implication of such mediators suggests that interruption or blunting of an inappropriate immune response has the potential to improve outcome. Although the manipulations of specific mediators in animal models may be promising, they may not transition well to the human clinical setting. However, continued reliance on experimental animal models of acute pancreatitis may be necessary to determine the underlying causes of disease. Full understanding of these basic mechanisms involves determining not only which mediators are present, but also closely documenting the kinetics of their appearance. Measurement of the inflammatory response may also serve to identify diagnostic markers for the presence of acute pancreatitis and provide insight into prognosis. Understanding the models, documenting the markers, and deciphering the mediators have the potential to improve treatment of acute pancreatitis.     

CC-chemokine activation in acute pancreatitis: enhanced release of monocyte chemoattractant protein-1 in patients with local and systemic complications

OBJECTIVE: Systemic leukocyte activation is claimed to trigger inflammatory response and remote organ dysfunction in acute pancreatitis. Chemokines are inflammatory mediators with potent leukocyte-activating properties and have been shown to be involved in the pathophysiological process of experimental acute pancreatitis. However, as little is known about their role in human disease we investigated local and systemic concentrations of different CC-chemokine members in patients with acute pancreatitis. PATIENTS AND METHODS: We included 68 patients with acute pancreatitis in the present study. Local complications in terms of necrosis were present in 37 (54%) patients of whom 21 (57%) developed pancreatic infections. Monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha (MIP-1alpha) and macrophage inflammatory protein-1beta (MIP-1beta) concentrations were measured daily over 2 weeks after study inclusion by ELISA in sera and lesser sac aspirates. RESULTS: MCP-1 serum concentrations showed a dramatic increase in patients who developed local complications and/or remote organ failure. Herein, a close correlation was found between the severity of remote organ failure and the degree of MCP-1 elevation. Multiple regression analysis identified pancreatic infections as well as renal and cardiocirculatory failure as independent variables associated with enhanced systemic MCP-1 release. MIP-1alpha levels remained unaffected by local complications and showed a significant increase only; if multiple organ dysfunction syndrome (MODS) developed or patients subsequently died. In contrast, MIP-1beta concentrations correlated with neither the presence nor the severity of any complication. Compared with systemic concentrations, local lesser sac aspirates revealed significantly higher levels of MCP-1, whereas MIP-1alpha and MIP-1beta were not different. CONCLUSIONS: Complicated acute pancreatitis is associated with significantly elevated local and systemic concentrations of the CC-chemokine MCP-1. Our results suggest that, among the CC-chemokine members investigated, MCP-1 might play a pivotal role in the pathological mechanism of complicated acute pancreatitis.     

Decreased HLA (human leucocyte antigen)-DR expression on peripheral blood monocytes predicts the development of organ failure in patients with acute pancreatitis

Immune suppression plays an important role in the pathogenesis of acute pancreatitis. Monocyte expression of HLA (human leucocyte antigen)-DR, a cellular marker of immune suppression, was determined in relation to the development of organ dysfunction in patients with acute pancreatitis. A total of 310 consecutive patients with acute pancreatitis, admitted to a university hospital within 72 h of pain onset, were studied; 194 (63%) had mild disease (group I), 87 (28%) had severe disease without organ dysfunction (group II), and 29 (9%) had severe disease with organ dysfunction (group III). HLA-DR expression, defined both as the proportion of monocytes that were HLA-DR-positive and as monocyte HLA-DR fluorescence intensity, was determined at admission, using whole-blood flow cytometry. Of the patients in group III, 13 (45%) developed organ dysfunction within 24 h of admission. The proportion of HLA-DR-positive monocytes and monocyte HLA-DR density were both related to the severity of pancreatitis (P<0.001 for linear trend). In predicting organ dysfunction, the sensitivity, specificity and positive-likelihood ratio for the proportion of HLA-DR-positive monocytes were 83% [95% CI (confidence interval) 64-94%], 72% (67-77%) and 3.0 respectively, and for monocyte HLA-DR density the respective values were 69% (49-85%), 84% (79-88%) and 4.3. In conclusion, monocyte HLA-DR expression predicts the development of organ dysfunction that occurs early in patients with acute pancreatitis.     

40例多器官衰竭时急性肾功能衰竭的临床分析

目的：探讨多器官衰竭（ＭＯＦ）时急性肾功能衰竭（ＡＲＦ）的更为有效的防治手段，防止和阻断其进一步发展，改善ＭＯＦ的预后。方法：对４０例ＭＯＦ合并ＡＲＦ的病例资料进行临床分析。结果：ＭＯＦ的主要原发病因是感染（７０．０％），其次是创伤（２２．５％），其它占７．５％；本组患者的病死率６５．０％，且随衰竭器官的数目增多而病死率升高。ＡＲＦ表现为少尿型８７．５％，非少尿型１２．５％。采用血液透析（ＨＤ）治疗２２例中存活１２例，死亡１０例，病死率５４．５％；非ＨＤ治疗１８例中存活２例，死亡１６例，病死率８８．９％，比较此两种治疗方法的疗效ＨＤ组明显高于非ＨＤ组（Ｐ＜０．０１）。结论：对于ＭＯＦ时ＡＲＦ的治疗，首先应针对各器官衰竭的治疗；积极有效地控制感染是抢救成功的关键；早期充分的血液净化是治疗的重要环节；辅助支持疗法，提高免疫功能，改善组织缺氧，禁止应用对肾脏有损害的药物，对改善本病的预后具有重要意义。     

Clinical relevance of caspase-1 activated cytokines in acute pancreatitis: high correlation of serum interleukin-18 with pancreatic necrosis and systemic complications

OBJECTIVES: There is recent experimental evidence that caspase-1 activation plays an instrumental role in the pathomechanism of severe acute pancreatitis. Besides interleukin-1beta, interleukin-18, a recently described proinflammatory cytokine, is cleaved into its biologically active form by caspase-1 as well. Interleukin-18 is known to have potent properties concerning the activation of the Th1-lymphocyte subset via costimulation of interferon-gamma production. In contrast to interleukin-1beta, little is known about the clinical impact of interleukin-18 in the course of acute pancreatitis. DESIGN: Cohort study comparing patients with mild and severe acute pancreatitis associated with local and systemic complications during the course of the disease. SETTING: Surgical and anesthesiological intensive care unit as well as wards of the department of general surgery. PATIENTS: We included 68 patients with acute pancreatitis in the present study. In terms of local complications, pancreatic necrosis was present in 37 patients, of whom 21 developed pancreatic infections. Systemic complications included pulmonary, renal, or cardiocirculatory insufficiency and were observed in 40, 18, and 25 patients, respectively. Severe multiple-organ dysfunction syndrome involving all three organ systems occurred in 18 patients, all suffering from pancreatic necrosis. INTERVENTIONS: Serum samples were collected over 14 consecutive days after study inclusion. Ascites or peripancreatic exudate was obtained by ultrasound-guided fine needle aspiration in 14 cases. Sera and local aspirates were stored at -70 degrees C until analysis. MEASUREMENTS AND RESULTS: Interleukin-18 and interferon-gamma were measured by commercially available enzyme-linked immunosorbent assays. Interleukin-18 concentrations were significantly increased after the fourth day of disease onset until the end of the observation period in patients who developed pancreatic necrosis and systemic complications such as pulmonary, renal, and cardiocirculatory failure as well as severe multiple-organ dysfunction syndrome. However, no correlation was found between the development of pancreatic infections and interleukin-18 concentrations. In contrast with interleukin-18, interferon-gamma concentrations did not show any significant difference with respect to the presence or absence of either systemic or local complications. Local interleukin-18 concentrations in ascites or peripancreatic exudate were up to 20-fold higher than systemic concentrations, whereas interferon-gamma concentrations did not differ. CONCLUSIONS: Serum interleukin-18 concentrations are significantly elevated in patients with acute pancreatitis complicated by pancreatic necrosis and remote organ failure. The present data suggest an important role of caspase-1 dependent cytokine activation in the pathomechanism of severe acute pancreatitis beyond the experimental setting. In this context, interleukin-18 may serve as a potential target for new therapeutic approaches.     

Immune dysfunction in the critically ill infant and child

Factors contributing to the high prevalence of immunodeficiency in the PICU population include conditions that lead to frequent requirement of intensive care, suppression of immunity secondary to an acute insult, and iatrogenic measures. The immunodeficiency observed in the critically ill correlates well with their susceptibility to infection and explains the high prevalence of nosocomial sepsis in the PICU--a major cause of morbidity and mortality in critically ill children. Dysactivation of the immune system during an acute insult, with the subsequent release of humoral mediators from activated immune cells, leads to tissue injury and may be involved in the pathogenesis of ARDS, DIC, capillary leak syndrome, and to the development of multiple organ system failure. Suggested approaches to correct the immunodeficiency in the critically ill include reconstitutional immunotherapy, mediator-inhibiting drugs, and mediator removal by plasma exchange. Intensivists should be aware of the phenomenon of immunodeficiency in the critically ill, be accordingly aggressive in diagnosing and treating infections, and avoid, as much as possible, measures that further suppress immunity.     

Activated protein C in severe acute pancreatitis without sepsis? Not just yet ...

Severe acute pancreatitis (SAP) is characterized by an unregulated systemic proinflammatory response secondary to activation of trypsin within the pancreatic tissue, resulting in multiple organ failure. This dysregulated inflammation leading to organ dysfunction also characterizes severe sepsis. Activated protein C (APC) has pleotropic effects on the immune, coagulation, inflammatory and apoptotic pathways, and has been postulated to benefit acute pancreatitis - although concerns of possible retroperitoneal bleeding remain. Currently, experimental studies and subgroup data on patients with pancreatitis from a randomized controlled trial of APC in severe sepsis form the literature on the possible role of APC in SAP. We review the first randomized controlled trial of APC in acute pancreatitis published in the present issue of Critical Care.     

Role of free radicals in the development of severe acute pancreatitis

Acute pancreatitis is an inflammatory disease which leads to acinar cell damage, interstitial edema, and hemorrhage. Some patients develop severe acute pancreatitis and result in multiple organ dysfunction syndrome. Acute pancreatitis is initiated by the activation of pancreatic enzyme in acinar cells. Following activation of trypsinogen into trypsin, local inflammation is initiated and activated inflammatory mediators are produced. Polymorphonuclear neutrophils, macrophages, and lymphocytes release lysosomal enzymes, oxygen free radicals, vasoactive substances, and proinflammatory mediators. In the course of the development of acute pancreatitis oxygen-free radicals and their derivatives play an important role as the molecular trigger in constituting lesions in the pancreas. Damaged acinar cells as well as activated neutrophils and macrophages produce large amount of oxygen radicals in acute pancreatitis. The hydrogen peroxide, superoxide, the hydroxyl radical, and singlet oxygen are key elements capable of cellular injury in acute pancreatitis. These highly reactive species cause various reactions, such as destruction of lipid membranes by peroxidation of fatty acids and destruction of lysosomal membranes. The oxygen radicals generated in the circulation might injure the capillary endothelium, and play an important role in accelerating the progression of acute pancreatitis. The imbalance of oxygen radical generating and oxygen radical scavenging processes is considered to lead to the cell injury in acute pancreatitis. These oxygen radicals are not only restricted in the pancreatic tissue, but involved in the systemic manifestation of the disease, particularly in the lungs, liver, and blood.     

Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis

Introduction  

Disturbed protein C (PC) pathway homeostasis might contribute to the development of multiple organ failure (MOF) in acute pancreatitis (AP). We therefore evaluated circulating levels of PC and activated protein C (APC), evaluated monocyte deactivation in AP patients, and determined the relationship of these parameters to MOF.     

Défaillance multiviscérale précoce associée à la pancréatite aiguë : stratégie thérapeutique chirurgicale ou conservatrice ?

The mortality of severe acute pancreatitis still ranges between 10% and 20%. Nowadays, infected pancreatic necrosis is the leading cause of death. Despite advances in intensive care therapy, however, early and worsening multi-system organ failure remains a source of substantial morbidity and still accounts for 20–50% of the deaths.News and hotspots.– The three interrelated pathophysiological mechanisms underlying glandular necrosis include the premature intra-acinar activation of pancreatic pro-enzymes, an early pancreatic microcirculatory impairment, and the excessive stimulation of immune effector cells. In recent years, the systemic inflammatory response syndrome and the relevant cascades of inflammatory mediators have been implicated as the key factor in the emergence of remote tissue damage. Early multi-system organ failure that supervenes in the first week is typically associated with a sterile necrotizing process. The correlation between pathomorphological and clinical severity and the similarity between their respective pathophysiological mechanisms are not straightforward, however. There are no pathophysiological, clinical or economical data to support the practice of debridement of sterile necrosis to prevent or to control early multi-system organ failure. This issue has never been addressed in a controlled study. Besides intensive care support, non-surgical therapeutic modalities including urgent endoscopic sphincterotomy for impacted stones, antibiotic prophylaxis for the prevention of pancreatic infection and early jejunal nutrition have been specifically developed hopefully to attenuate multiple organ failure, to obviate the need of surgical drainage and to improve survival. Fine needle aspiration of necrotic areas must be incorporated in any conservative therapeutic strategy in order not to jeopardize those with infected necrosis that remains an absolute indication for drainage.Perspectives.– There is ample experimental and pathophysiological evidence in favour of immunomodulatory therapy in severe acute pancreatitis. The administration of one or several antagonists of inflammatory mediators possibly combined with a protease inhibitor may at last provide the opportunity to interfere with the two major determinants of prognosis: the severity of multiple organ failure and the extent of necrotic areas that creates the culture medium for bacterial superinfection. These benefits remain to be substantiated in a controlled study, however.     

Recent advances in the surgical management of necrotizing pancreatitis

PURPOSE OF REVIEW: To summarize advances and new concepts in the surgical management of necrotizing pancreatitis published within the past year with emphasis on the evolving importance of the recognition of abdominal compartment syndrome as a significant contributor to early development of organ failure. RECENT FINDINGS: Underdiagnosed and untreated, abdominal compartment syndrome is a potential contributing factor to the development of early organ failure in patients with severe acute pancreatitis and warrants routine measurement of intra-abdominal pressure in patients treated for severe pancreatitis. The current estimate of the prevalence of intra-abdominal hypertension in severe acute pancreatitis is about 40%, with about 10% overall developing abdominal compartment syndrome, associated with increased hospital mortality rates. Early surgical decompression without exploring the pancreas further seems to be the most effective treatment. Primary fascial closure of the abdominal wall following abdominal decompression can be attempted, but in most cases the prolonged inflammatory process in the abdomen and the risk of recurrent abdominal compartment syndrome favors use of gradual closure or delayed reconstruction of the abdominal wall. SUMMARY: Recent studies confirm the overall validity of the established surgical principles for necrotizing pancreatitis: delayed necrosectomy in patients with infected peripancreatic necrosis, mostly nonoperative management of sterile necrosis, and delayed cholecystectomy in severe gallstone-associated pancreatitis. The role of abdominal compartment syndrome as an important contributing factor to early development of multiple organ failure and the potential benefit of surgical decompression are gaining support from recent reports and should be carefully assessed in future studies.     

Acute pancreatitis with organ dysfunction associates with abnormal blood lymphocyte signaling: controlled laboratory study

Introduction  

Severe acute pancreatitis is associated with systemic inflammation, compensatory immune suppression, secondary infections, vital organ dysfunction, and death.     

重症急性胆管炎后多器官衰竭的危险因素分析

分析了２００例重症急性胆管炎（ＡＣＳＴ）及其中７０例并发多器官衰竭（ＭＯＦ）病例的临床资料，旨在研究重症急性胆管炎并发ＭＯＦ的危险因素。结果发现：早期休克、营养不良、肺部感染、败血症及长期胆道梗阻等病例的ＭＯＦ发生率明显增高。作者认为早期监护高危患者和综合治疗是降低ＭＯＦ病死率的关键。     

Role of apoptosis in severe acute pancreatitis

The role of apoptosis in a severe acute pancreatitis is recently given the most attention, but it is hardly known in a clinical study. We show three assumptions between apoptosis and the pathophysiological mechanisms of severe acute pancreatitis in this paragraph. First, the apoptosis of pancreatic acinar cell might prevent from a worsening in acute pancreatitis due to diminish leakage of pancreatic enzyme and extension of inflammation. Secondly, impairment cellular immunity due to peripheral lymphocyte apoptosis might be linked to the development of subsequent infectious complications in acute pancreatitis. Third, apoptosis in various major organs might be involved in the mechanism of multiple organs failure in acute pancreatitis. These findings might lead the new development in the therapeutic strategy of acute pancreatitis.     

Liver injury associated with acute pancreatitis: The current status of clinical evaluation and involved mechanisms

Acute pancreatitis (AP) is a very common acute disease, and the mortality rate of severe AP (SAP) is between 15% and 35%. The main causes of death are multiple organ dysfunction syndrome and infections. The mortality rate of patients with SAP related to liver failure is as high as 83%, and approximately 5% of the SAP patients have fulminant liver failure. Liver function is closely related to the progression and prognosis of AP. In this review, we aim to elaborate on the clinical manifestations and mechanism of liver injury in patients with AP.     

A patient with severe acute pancreatitis successfully treated with a new critical care procedure.

It has been accepted widely that excessive humoral mediators play important roles in the pathogenesis of organ failure in patients with severe acute pancreatitis (SAP) and that infection of the pancreas due to bacterial translocation (BT) is the most frequent cause of death in SAP. On the other hand, it has been reported that continuous hemodiafiltration (CHDF) removes humoral mediators on hypercytokinemic patients such as those with systemic inflammatory response syndrome. Furthermore, several clinical studies have demonstrated that selective digestive decontamination (SDD) effectively eliminates aerobic Gram-negative bacteria from the intestinal tract and reduces the incidence of septic complications in SAP. Herein we report a case of SAP who was treated successfully with intensive care including CHDF and SDD. Thus, this case report suggests that CHDF aimed at removing causative humoral mediators and SDD for the prevention of BT are useful new tools for the management of SAP.     

Coagulation/fibrinolysis abnormality and vascular endothelial damage in the pathogenesis of thrombocytopenic multiple organ failure

OBJECTIVE: Until recently, attention has been directed to disseminated intravascular coagulation as a cause of multiple organ failure (MOF). On the other hand, it has now become clear that humoral mediators play important roles in the pathogenesis of MOF. Therefore, we performed the present study in patients with thrombocytopenic MOF to investigate the relationship between various humoral mediators and vascular endothelial damage reported to be triggered by such humoral mediators in the pathogenesis of MOF. DESIGN: A retrospective clinical study. SETTING: Intensive care unit of a university hospital. PATIENTS: The study included 18 thrombocytopenic patients whose conditions progressed to septic MOF (MOF group) and 20 others who did not progress to MOF (non-MOF group). The MOF group and non-MOF group were also presented with infection and with platelet counts of <100,000/mm3. MEASUREMENTS AND MAIN RESULTS: The MOF group had fibrinolysis abnormality, as indicated by increased plasminogen activator inhibitor-1 level. On the other hand, the MOF group had increased polymorphonuclear elastase and polymorphonuclear-mediated fibrinogen degradation product levels with consequent prolonged elevation of thrombomodulin. In addition, both polymorphonuclear elastase and polymorphonuclear-fibrinogen degradation products were significantly positively correlated with thrombomodulin in the MOF group, but no such positive correlation was observed between interleukin-6 or plasminogen activator inhibitor-1 and thrombomodulin. In the non-MOF group, on the other hand, thrombomodulin exhibited no significant positive correlation with polymorphonuclear elastase, polymorphonuclear-fibrinogen degradation products, interleukin-6, or plasminogen activator inhibitor-1. CONCLUSIONS: Our study provided evidence that vascular endothelial damage was the primary cause of organ failures in patients with thrombocytopenic MOF and that humoral mediators played a major role in the development of vascular endothelial damage in such patients. These results suggest that it is important to treat thrombocytopenic MOF as a condition of vascular endothelial damage, with weight placed on countermeasures against disorders of humoral mediators.     

腹部外科多器官功能衰竭68例患者的救治

报道11年间明确诊断为腹部外科多器官功能衰竭(MOF)的患者68例,提出了腹部外科MOF的临床特点、触发因素、首发衰竭器官、各个脏器衰竭发生频度、死亡原因和病死率及MOF的预防和现代救治措施.资料分析结果显示,腹部外科MOF的触发因素为严重感染、败血症、重度多发伤和急诊腹部外科大手术等.腹部外科MOF治疗的关键是要切实做到早期识别、早期检查、早期诊断和早期治疗.救治结果存活17例,死亡51例.作者提出MOF一旦发病要给予强有力的“四大一支持”综合措施的新疗法.本组18例MOF患者实施“四大一支持”综合疗法,15例获救治成功,该疗法具有实用、有效的价值.