系统评价我国重症急性胰腺炎患者继发胰腺感染的危险因素

目的：系统评价我国重症急性胰腺炎（severe acute pancreatitis,SAP）继发胰腺感染的危险因素,为临床预防和控制感染提供依据。方法：检索中国知网（CNKI）、维普、万方、中国生物医药、PubMed、Cochrane Library、EMbase等数据库,收集关于我国SAP继发胰腺感染危险因素的病例对照研究,检索时间均为数据库建库至2020年10月31。由2名研究者按照纳入和排除标准筛选文献并提取资料,使用RevMan5.3件进行Meta分析。结果：共纳入20篇文献,2 393例患者,其中胰腺感染组827例,非感染组1 566例。Meta分析结果显示,SAP类型为胆源型（Or=1.42,95% CI：1.11~1.81）、入院时APACHE-Ⅱ评分（MD=2.44,95% CI：1.79~3.08）、入院时Ranson评分（MD=0.74,95% CI：0.54~0.94）、禁食>15 d（OR=3.02,95% CI：1.69~5.40）、胰腺坏死（OR=3.91,95% CI：1.57~3.91）、胃肠功能障碍>5 d（OR=5.49,95% CI：.91~7.70）、糖尿病并发症（OR=3.31,95% CI：2.10~5.21）、机械通气（OR=1.94,95% CI：1.53~2.45）、机械通气时间（MD=9.86,95% CI：9.15~10.56）、外科手术治疗（OR=4.31,95% CI：2.90~6.41）、低氧血症（OR=3.36,95% CI：2.75~4.10）、SIRS（OR=3.84,95% CI：2.55~5.77）、MODS（OR=4.19,95% CI：2.79~6.30）、血清白蛋白（MD=-8.51,95% CI：－9.21~－7.82）、血清肌酐（MD=110.53,95% CI：78.25~142.82）和血钙水平（MD=－0.29,95% CI：－0.37~－0.21）是SAP继发胰腺感染的危险因素（P<0.05）。结论：临床应针对SAP继发胰腺感染危险因素早期予以预防用抗菌药物,以改善预后。     

69例急性重症胰腺炎的非手术治疗疗效评价

目的探讨急性重症胰腺炎的非手术治疗疗效评价。方法回顾分析69例急性重症胰腺炎的临床资料及早期内科非手术综合治疗效果。结果治疗后无并发症痊愈出院43例。治疗过程中出现并发症依次为ARDS、左心衰、胰腺假性囊肿、胰腺脓肿。转至外科手术治疗4例,死亡3例。结论急性重症胰腺炎目前主张采取早期内科非手术综合治疗,加强首发器官衰竭的治疗及并发的多脏器功能衰竭的系统监控,对于提高治愈率,降低脏器功能衰竭发生率和病死率十分重要。     

重症急性胰腺炎并发症的诊治

目的 探讨重症急性胰腺炎发生并发症的诊断与治疗。方法 对1987-01～1998-04收治的27例重症急性(?)腺炎所致的各类并发症66例作回顾性分析。结果 呼吸窘迫综合征、多器官功能障碍综合征是致死的主要原因。胸腔积液(?)胰腺脓肿、假性褒肿、肠瘘、胰瘘、腹腔内出血等并发症常见。胰外损害的程度以及手术时机和术式与并发症的发生密切(?)关。结论 重症急性胰腺炎的诊断一旦成立,并发症的防治即应开始,减轻胰外损害是治疗的关键。     

Antibiotics in severe acute pancreatitis

Acute pancreatitis (AP) is a local inflammatory response with systemic effects and an adverse evolution in 20% of cases. Its mortality rate is 5–10% in sterile and 15–40% in infected pancreatic necrosis. Infection is widely accepted as the main reason of death in AP. The evidence to enable a recommendation about antibiotic prophylaxis against infection of pancreatic necrosis is conflicting and difficult to interpret. Up to date, there is no evidence that supports the routine use of antibiotic prophylaxis in patients with severe AP. Treatment on demand seems to be the better option, avoiding excessive treatment and selection of bacterial. In infected acute pancreatitis, antibiotics of choice are imipenem, meronem or tigecycline in patients allergic to beta-lactams. Also fluconazole must be given in determinate clinical situations.     

Current pharmacotherapeutic recommendations for acute pancreatitis

Disease severity in patients with acute pancreatitis varies from mild disease with minimal morbidity to severe disease in which a whole spectrum of local and systemic complications may occur. Infectious complications frequently arise, and pancreatic necrosis in particular is an important risk factor for mortality. Several strategies have been investigated to stop the progression of organ dysfunction, targeting different steps in the pathogenesis, but none of these have proved beneficial. In recent years, the widespread use of prophylactic antibiotics has also been in question, as one blinded study could not demonstrate an advantage. Better risk stratification methods should improve the design of future trials, so that only patients with a high probability of complications can be studied.     

选择性脾动脉药物灌注治疗重症胰腺炎

目的　探讨脾动脉药物灌注治疗重症胰腺炎的治疗方法。方法　回顾性分析比较 4 0例重症胰腺炎患者的治疗结果 ,其中保守治疗、手术治疗 19例 ,选择性脾动脉药物灌注治疗 2 1例。结果　保守治疗、手术治疗组继发感染率 5 7 8% ,死亡率 5 2 6 %。选择性脾动脉药物灌注治疗组继发感染率 9 5 %、死亡率 4 7%。两组相比 (P <0 .0 1)差异有显著性意义。两组比较APACHEII评分、腹痛缓解、肠功能恢复及器官功能衰竭仍有显著差异 (P <0 .0 5 )。结论　选择性脾动脉药物灌注治疗胰腺炎是救治重症胰腺炎的一种理想方法并应推广应用     

Protective effect of the combined treatment of pancreatic and neutrophil elastase inhibitors on acute pancreatitis elicited by lipopolysaccharide in rats given intraductal injection of taurocholate plus trypsin

A severe acute pancreatitis was produced by intraperitoneal injection of lipopolysaccharide (LPS) in rats with preexisting hemorrhagic and necrotizing pancreatitis induced by retrograde injection of a 5% taurocholate plus 1% trypsin solution into the pancreatic duct. Mortality and time-course changes in pancreatic, hepatic, renal and pulmonary functions, and organ myeloperoxidase (MPO) levels were examined in this model. LPS at an intraperitoneal dose of 30 mg/kg, which scarcely caused death and had no marked effect on serum parameters and organ MPO levels in rats without pancreatitis, increased the mortality in rats with taurocholate plus trypsin-induced pancreatitis. Pancreatic weight and ascitic volume increased in rats with taurocholate plus trypsin-induced pancreatitis regardless of the presence or absence of LPS. Serum amylase and lipase levels were also significantly increased in rats with induced pancreatitis, but was higher in the group given LPS. Serum glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), blood urea nitrogen (BUN) and creatinine levels were significantly elevated in LPS-treated rats with induced pancreatitis, whereas levels in rats with induced pancreatitis not given LPS were only slightly elevated. Renal weight was also significantly increased in rats with induced pancreatitis despite the presence or absence of LPS. In LPS-treated rats with induced pancreatitis, the arterial oxygen pressure, pulmonary weight and pulmonary MPO level were significantly elevated. However, the MPO level in the kidney in these rats was not different from that in control rats, indicating that the renal dysfunction was not produced by the infiltration of neutrophils into the kidney. Increase in the pancreatic MPO level was observed in rats with induced pancreatitis, but combination treatment with LPS did not raise it. Protective effects of prophylactic treatment of 2-(3-methylsulfonylamino-2-oxo-6-phenyl-1,2-dihydro-1-pyridyl)-N-(3,3,3-trifluoro-1-isopropyl-2-oxopropyl)acetamide (compound 1), a neutrophil elastase inhibitor, and trifluoroacetyl-L-lysyl-L-alaninanilide hydrochloride (compound 2), a pancreatic elastase inhibitor, on mortality were also examined in this model. Results were compared with that of the combined treatment of compound 1 and compound 2. In LPS-treated rats with taurocholate plus trypsin-induced pancreatitis, the combined treatment of compound 1 (2 mg/kg/h) and compound 2 (30 mg/kg/h) significantly reduced mortality, whereas single treatment of compound 1 or compound 2 did not show the beneficial effect. These results suggest that marked hepatic and renal dysfunction accompanies pancreatitis in this pancreatitis model rats, which may be good models for acute pancreatitis in humans. It is also suggested that neutrophil and pancreatic elastases may be synergistically involved in the pathogenesis of acute pancreatitis in this model. Received: 24 November 1997 / Accepted: 10 February 1998     

国产美罗培南与进口亚胺培南/西司他丁预防重症急性胰腺炎腹腔感染的随机对照研究

目的:评价国产美罗培南对重症急性胰腺炎患者腹腔感染预防的有效性和安全性。方法:采用随机、双盲、对照开放试验。临床确诊重症急性胰腺炎的患者随机分为试验组与对照组,试验组应用国产美罗培南500mg,tid,对照组应用进口亚胺培南/西司他丁500mg,tid,疗程均为7～14d。记录2组患者生命体征、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)评分、血常规、肝肾功能以及恶心、呕吐、腹痛、腹胀等,统计患者感染发生率及死亡率。结果:试验组与对照组均有28例患者纳入本研究,各有27、25例可进行疗效评价,各组有25例可进行安全性评价。腹腔感染发生率试验组为14.8%,对照组为16.0%(P>0.05);不良反应发生率试验组为20.0%,对照组为24.0%(P>0.05)。结论:在重症急性胰腺炎预防性应用抗菌药物治疗中,单用国产美罗培南可达到进口亚胺培南/西司他丁同样的效果。     

Hyperlipidemia induced by a cholesterol-rich diet aggravates necrotizing pancreatitis in rats

The aim of the present study was to investigate whether hyperlipidemia can cause acute pancreatitis or alter its severity. Male Wistar rats were fed a 3% cholesterol-enriched diet or a normal diet for 16 weeks. Edematous and necrotizing pancreatitis was induced with 3x75 mug/kg body weight of cholecystokinin s.c. and 2x2 g/kg body weight of L-arginine i.p., respectively, in separate groups of normal and hyperlipidemic rats. The severity of the pancreatitis was assessed. We studied the influence of hyperlipidemia on the formation of oxygen-derived free radicals, endogenous scavengers, nitric oxide synthases (NOS), peroxynitrite (ONOO(-)), heat shock protein 72 (HSP72) and nuclear factor-kappa B (NF-kappaB) activation in the pancreas during acute edematous and necrotizing pancreatitis. Hyperlipidemia did not worsen edematous, but aggravated necrotizing pancreatitis. The cholesterol-enriched diet significantly reduced the catalase and Mn-superoxide dismutase (SOD) and constitutive NOS (cNOS) activities and increased the inducible NOS (iNOS) in the pancreas relative to those in the rats on the normal diet. The pancreatic nitrotyrosine level, as a marker of ONOO(-), and the NF-kappaB DNA-binding activity in the pancreas, were significantly elevated in the cholesterol-fed rats. The pancreatic HSP72 expression during necrotizing pancreatitis was not influenced by the hyperlipidemia. The pancreatic Mn-SOD, Cu, Zn-SOD, glutathione peroxidase, total glutathione and cNOS activities were significantly reduced, while the catalase, iNOS and NF-kappaB DNA-binding activities were significantly increased in the animals with necrotizing pancreatitis on the cholesterol diet as compared with those with pancreatitis and receiving the normal diet. Hyperlipidemia induced with this cholesterol-enriched diet leads to decreases in endogenous scavenger and cNOS activities, results in iNOS and NF-kappaB activation and stimulates ONOO(-) generation in the pancreas, which may be responsible for the aggravation of acute necrotizing pancreatitis.     

Pancreatic injury following acute methanol poisoning

BACKGROUND: Methanol ingestion is a cause of potentially life-threatening poisoning with numerous systemic manifestations. Clinicians may overlook the possibility of acute pancreatitis in this setting. The objective of this paper is to document the incidence of this complication in a series of 22 patients and to discuss the respective role of methanol and ethanol in its pathogenesis. CASE REPORT: A 54-year-old woman developed acute necrotizing pancreatitis following acute methanol poisoning. She was treated by hemodialysis, ethanol infusion, and folinic acid, but, despite maximal supportive therapy, she died from multiple organ failure 54 hours after the ingestion. CASE SERIES: In a series of 22 consecutive patients admitted with a diagnosis of acute methanol poisoning, we found evidence of pancreatic damage in 11 patients. The abnormalities were present from admission and before ethanol therapy in 7 cases and developed after ethanol therapy in 4 cases. Seven patients had a history of chronic ethanol abuse, but no patient had previously suffered from acute or chronic pancreatitis. Three patients presented moderate-to-severe acute pancreatitis according to clinical and radiological criteria and required aggressive supportive therapy including peritoneal dialysis. One patient died from the direct consequences of acute necrotizing pancreatitis and 2 fully recovered from this event. Three patients evolved to brain death; autopsy revealed hemorrhagic lesions in the pancreas in only 1 case. CONCLUSIONS: Clinical, biological, and radiographic signs of acute pancreatic injury may be more common than previously realized. Acute methanol poisoning appears to produce pancreatic injury, although antidotal treatment with ethanol or prior chronic ethanol abuse may be contributing factors. Because ethanol treatment may complicate the pancreatic injury, fomepizole (4-methylpyrazole) may be the preferable antidote in acute methanol poisoning.     

胰管持续梗阻促进急性胰腺炎的发展

为研究胰管高压本身在胰腺炎发病机制方面的作用,本实验在狗身上,观察胰管梗阻时间长短对胰腺炎症程度的影响。胰管梗阻３０ｍｉｎ者,胰腺炎症最轻,死亡率最低（１／８）;梗阻２４ｈ者,胰腺炎症较重,死亡率较高（２／６）;持续性梗阻者,胰腺炎最重,死亡率最高（６／６）。本实验进一步证明胰管梗阻在促进急性胰腺炎的发展方面起着重要的作用。     

Optimising outcomes in acute pancreatitis

Acute pancreatitis is a common cause for presentation to emergency departments. Common causes in Western societies include biliary pancreatitis and alcohol (the latter in the setting of chronic pancreatitis). Acute pancreatitis also follows endoscopic retrograde pancreatography in 5 to 10% of patients, a group that could potentially benefit from prophylactic treatment. Although episodes of pancreatitis usually run a relatively benign course, up to 20% of patients have more severe disease, and this group has significant morbidity and mortality. Therefore, attempts have been made to identify, at or soon after presentation, those patients likely to have a poor outcome and to channel resources to this group. The mainstay of treatment is aggressive support and monitoring of those patients likely to have a poor outcome. Pharmacotherapy for acute pancreatitis (both prophylactic and in the acute setting) has been generally disappointing. Efforts initially focused on protease inhibitors, of which gabexate shows some promise as a prophylactic agent. Agents that suppress pancreatic secretion have produced disappointing results in human studies. Infection of pancreatic necrosis is associated with high mortality and requires surgical intervention. In view of the seriousness of infected necrosis, the use of prophylactic antibacterials such as carbapenems and quinolones has been advocated in the setting of pancreatic necrosis. Similarly, data are accumulating to support the use of prophylactic antifungal therapy. Recently, it has become apparent that the intense inflammatory response associated with acute pancreatitis is responsible for much of the local and systemic damage. With this realisation, future efforts in pharmacotherapy are likely to focus on suppression or antagonism of pro-inflammatory cytokines and other inflammatory mediators. Similarly, animal studies have demonstrated the importance of oxidative stress in acute pancreatitis, although to date there is a paucity of information regarding the efficacy of antioxidants. Although the clinical course for most patients with acute pancreatitis is mild, severe acute pancreatitis continues to be a clinical challenge, requiring a multidisciplinary approach of physician, intensivist and surgeon.     

Quality assurance of sphincterotomy: A prospective single-centre survey

Quality assurance becomes an increasingly important part of clinical medicine and of the field of endoscopy. Endoscopic sphincterotomy is associated with a fairly high complication rate. We aimed to assess our quality of sphincterotomy for benchmarking by using a prospective electronic database registry, and to identify potential risk factors for post-interventional complications. Over 2 years, 471 sphincterotomies were performed in a single tertiary referral centre. Patient- and procedure-related variables were prospectively recorded with the support of a multi-centre international sphincterotomy registry. Multivariate analysis was performed. The overall post-interventional complication rate was 9.3%. Pancreatitis happened in 5.5%, bleeding in 2.1%, perforation in 1.3%, and cholangitis in 0.4%. In the multivariate analysis following variables remained highly significant and predictive for complications: ‘papilla only in lateral view’ (p=0.001), antiplatelet therapy (p=0.024), and opacification with contrast up to the pancreatic tail (p=0.001). The primary success rate of sphincterotomy was 95.1%. The rate of post-interventional pancreatitis did not differ significantly regardless of the presence of prophylactic pancreatic stent (p=0.56). The outcome of sphincterotomy in our centre matches with literature data. The extent of pancreatic duct opacification has an influence on the pancreatitis rate. Prevention of pancreatitis by inserting pancreatic stents is not confirmed.     

手术对急性出血坏死性胰腺炎患者预后的影响

目的 探讨外科手术对急性出血坏死性胰腺炎患者预后的影响.方法 对66例急性出血坏死性胰腺炎患者的临床资料进行回顾分析,分为手术组(50例)和保守治疗组(16例),比较两组继发感染率、治愈率、住院时间、住院总费用的差异.结果 手术组患者继发感染率、治愈率、住院时间、住院总费用均显著优于保守治疗组(x2 =5.38,5.56,t =24.65,6.46,均P＜0.05).结论 积极的手术治疗可明显改善急性出血坏死性胰腺炎预后,降低医疗费用.     

胆源性胰腺炎的诊断与外科手术治疗

目的探讨胆源性胰腺炎的临床诊断和手术治疗时机和方法。方法选取本院收治的胆源性胰腺炎病例90例,对其临床资料进行回顾性分析。结果轻症胰腺炎治愈率明显高于重症胰腺炎;死亡5例,均为重症胰腺炎,其中早期手术2例分别死于多脏器功能衰竭和急性呼吸窘迫综合征,晚期手术3例皆死于由于术后继发腹腔严重感染所引发的多脏器功能衰竭;9例出现并发症,早期手术并发症发生率明显高于晚期手术。结论胆源性胰腺炎诊断可根据患者的临床表现结合B超以及CT检查,治疗时应根据患者的具体情况选择手术时机和手术方案。     

Diagnostic and surgical procedures in acute necrotizing pancreatitis (ANP).

The main subject of considerations is acute necrotizing pancreatitis, based on the authors opinion and literature. Frequency of the necrosis in acute pancreatitis is established in between 7-15%. Because of very severe and often lethal complications these patients need special surgical attention. Enhanced CT is the most valuable diagnostic procedure to visualize the extend of pancreatic necrosis. There is no common agreement upon the mode of treatment except from that infected necrotizing pancreatitis should be operated. Indications for surgical treatment with particular analysis to necrosectomy and laparostomy is discussed.     

多层螺旋CT在急性胰腺炎诊断中的应用价值

目的探讨多层螺旋CT对急性胰腺炎的诊断应用价值。方法对2008年1月～2010年12月住院的急性胰腺炎患者经手术病理证实和CT复查确诊的63例患者的临床资料作回顾性分析,全部病例均做腹部平扫,5例做增强扫描。结果胰腺局部或弥漫性肿大,胰腺边缘模糊及胰周积液是急性胰腺炎常见的CT征象,胰腺密度不均匀,其内见斑片状低密度灶和高密度出血是急性出血坏死性胰腺炎的特征表现。结论多层螺旋CT检查对急性胰腺炎有较高的诊断价值,不仅能明确诊断,而且有助于临床定量,可发现并发症和判断预后。     

Prevention effects of ND-07, a novel drug candidate with a potent antioxidative action and anti-inflammatory action, in animal models of severe acute pancreatitis

Oxidative stress and inflammation both play major roles in the development of the acute pancreatitis. Currently, a pancreatic enzyme inhibitor with limited efficacy is only clinically available in a few countries, and antioxidants or non-steroidal anti-inflammatory drugs (NSAIDs) provide only partial tissue protection in acute pancreatitis animal models. Here, we introduce a new drug candidate for treating acute pancreatitis named ND-07 [chemical name: 2-acetoxy-5-(2-4-(trifluoromethyl)-phenethylamino)-benzoic acid] that exhibits both potent antioxidative and anti-inflammatory activities. In an electron spin resonance (ESR) study, ND-07 almost blocked hydroxyl radical generation as low as 0.05 μM and significantly suppressed DNA oxidation and cell death in a lipopolysaccharide (LPS)-stimulated pancreatic cell line. In a cerulein plus LPS-induced acute pancreatitis model, ND-07 pretreatment showed significant tissue protective effects, with reductions of serum amylase and lipase levels and pancreatic wet weights. ND-07 not only diminished the plasma levels of malondialdehyde (MDA) and nitric oxide but also significantly decreased prostaglandin E? (PGE?) and expression of tumor necrotizing factor-alpha (TNF-α) in the pancreatic tissue. In a severe acute necrotizing pancreatitis model induced by a choline deficient, ethionine-supplemented (CDE) diet, ND-07 dramatically protected the mortality even without any death, providing attenuation of pancreas, lung, and liver damages as well as the reductions in serum levels of lactate dehydrogenase (LDH), amylase and lipase, MDA levels in the plasma and pancreatic tissues, plasma levels of TNF-α, and interleukin-1 (IL-1β). These findings suggest that current dual synergistic action mechanisms of ND-07 might provide a superior protection for acute pancreatitis than conventional drug treatments.     

Systematic review: nutritional support in acute pancreatitis

Background  There has been controversy concerning the merits of enteral and parenteral nutrition compared with no supplementary nutrition in the management of patients with acute pancreatitis.
Aim  To perform a systematic review of the data from randomized controlled trials (RCTs) in acute pancreatitis that compares enteral nutrition with no supplementary nutrition, parenteral nutrition with no supplementary nutrition and enteral nutrition with parenteral nutrition.
Methods  A search was undertaken in the MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials.
Results  Fifteen RCTs were included. Enteral nutrition, when compared with no supplementary nutrition, was associated with no significant change in infectious complications: ratio of relative risks (RR) 0.56, 95% confidence interval (CI) 0.07–4.32, P  = 0.58, but a significant reduction in mortality: ratio of RR 0.22, 95% CI 0.07–0.70, P  = 0.01. Parenteral nutrition, when compared with no supplementary nutrition, was associated with no significant change in infectious complications: RR 1.36, 95% CI 0.18–10.40; P  = 0.77, but a significant reduction in mortality: RR 0.36, 95% CI 0.13–0.97, P  = 0.04. Enteral nutrition, when compared with parenteral nutrition, was associated with a significant reduction in infectious complications: RR 0.41, 95% CI 0.30–0.57, P  < 0.001, but no significant change in mortality: RR 0.60, 95% CI 0.32–1.14, P  = 0.12.
Conclusions  The use of either enteral or parenteral nutrition, in comparison with no supplementary nutrition, is associated with a lower risk of death in acute pancreatitis. Enteral nutrition is associated with a lower risk of infectious complications compared with parenteral nutrition.     

24例急性重症胰腺炎治疗分析

目的对急性重症胰腺炎患者进行非手术治疗,并观察治疗进展,以便对治疗方法进行临床推广。方法对本院2009年6月～2011年6月收治的24例急性重症胰腺炎患者进行非手术治疗,包括使用抗生素、胰腺分泌抑制类药品、补充体液、调整体内酸碱平衡紊乱、全肠胃营养以及对治疗过程中出现的器官衰竭给予强心剂、输氧等治疗。结果对24例患者的治疗效果进行观察,其中66.7%的患者明显好转或治愈。结论急性重症胰腺炎患者进行非手术治疗相比同类治疗效果明显,尤其是早期发病患者,及时治疗可有效提高患者的治愈率。