Pathogenesis and prevention of early pancreatic infection in experimental acute necrotizing pancreatitis.

OBJECTIVE: The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis. BACKGROUND: Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon. METHODS: Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney. RESULTS: The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics. CONCLUSIONS: Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis.     

Acute pancreatic necrosis complicated by infection and gastro-intestinal translocation: pathogenesis correlation and therapeutic implication

The authors define pathogenetics correlations as a acute necrotizing pancreatitis complicated by infection and bacterial translocation. Acute necrotizing pancreatitis infection occurs for gastrointestinal bacterial translocation due to structural and functional modifications of intestinal mucosa. These modifications are results of mucosa ischemic-reperfusion system caused by systemic emodynamic instability in micro- and macro-circulation of splanchnic district. Emodynamic systemic instability has a central role in different multiple physiopathologic phenomena (ipovolemic shock; pancreatic shock, SIRS), which is caused by acute pancreatic necrosis and carries to common way established by severe systemics emodinamics modifications; these changes promote growth of adverse events which conduce by means of process previously described to bacterial translocation and infection of acute pancreatic necrosis. Indeed, emodynamic systemic instability of any etiology, can determine for one way bacterial translocation and on the other acute ischemic pancreatitis; both phenomena concur lead to cause beginning of acute necrotizing pancreatitis complicated by infection. The authors confirm that improved knowledge of acute pancreatic necrosis complicated by infection and own pathogenetic correlations with bacterial translocation, allows the realization of therapeutic measures aimed to prophylaxis of infection of acute pancreatic necrosis. Central emodynamic stability regularization of splanchnic perfusion and antibiotic prophylaxis, have a central role in prophylaxis of infection of acute pancreatic necrosis. Antibiotic is given by systemic (imipenem e.v.) and selective decontamination of gastrointestinal tract (SDD). SDD provides for oral antibiotic prophylaxis (PTA protocol) and systemic antibiotic prophylaxis (cefotaxime and gentamicin), in addition to microbiologic and gastrointestinal monitoring. If on the one hand the role of SDD about mortality reduction is not clear, however, on the other it is well recognized capacity of reduction the intercurrents and pulmonary infections. Other Authors think that SDD is insignificant on early mortality, whereas, is a good option to reduce late and overall mortality of acute pancreatic necrosis complicated by infection.     

重症急性胰腺炎继发胰腺感染的危险因素和感染特点分析

目的 研究重症急性胰腺炎继发胰腺感染的危险因素和感染特点.方法 采用1∶1配对病例对照研究,收集49对病例(SPI组)和对照(NSPI组),危险因素筛选用条件Logistic回归分析.结果 (1)单因素分析中筛出7项危险因素,其中低蛋白血症时间长、中心静脉置管时间长、激素经多因素分析与继发的胰腺感染相关.(2)SPI组胰腺脓肿居首位;胰腺感染发生在2周内的占22.5%,4周及其以后的占71.4%.(3)SPI组总共培养出病原菌81株(肠道菌占43.2%),革兰阴性菌、革兰阳性菌、真菌分别占55.6%、27.2%、17.3%.结论 长时间低蛋白血症、长时间中心静脉置管和激素是继发胰腺感染的独立危险因素.革兰阴性菌是继发胰腺感染的常见病原菌.     

Prophylactic antibiotics alter the bacteriology of infected necrosis in severe acute pancreatitis

BACKGROUND: Use of appropriate prophylactic antibiotics has been shown to decrease infectious complications and mortality rate in patients with severe acute pancreatitis, but its influence on the bacteriology of secondary pancreatic infection is poorly defined. STUDY DESIGN: Operative cultures from 61 consecutive patients with pancreatic necrosis treated during routine prophylactic antibiotic use (1993-2001) were compared with 34 consecutive patients with necrosis treated before routine antibiotic use (1977-1992). RESULTS: The two groups of patients were similar in demographics, etiology of pancreatitis, and severity of illness. All patients in the antibiotic group received prophylactic antibiotics compared with only 38% (13 of 34) in the control group. Routine broad-spectrum prophylactic antibiotics altered the bacteriology of secondary pancreatic infection in severe acute pancreatitis from predominantly gram-negative coliforms (56% versus 26%, p = 0.005) to predominately gram-positive organisms (23% versus 52%, p = 0.009) without a significant increase in either the rate of beta-lactam resistance or fungal infections. The overall hospital stay in patients treated with prophylactic antibiotics was significantly reduced (61 +/- 24 days versus 41 +/- 28 days, p = 0.002), and there was a trend toward a decline in mortality rate in the antibiotic treatment group. CONCLUSION: Routine broad-spectrum prophylactic antibiotic use has altered the bacteriology of secondary pancreatic infection in severe acute pancreatitis from predominantly gram-negative coliforms to predominantly gram-positive organisms without altering the rate of beta-lactam resistance or fungal superinfection.     

抗菌药物对预防重症急性胰腺炎感染的作用

为探讨抗菌药物对预防重症急性胰腺炎感染的作用，作者对１９９０年１０月至１９９５年３月收治的１０７例重症急性胰腺炎给予预防性使用环丙沙星加甲硝唑。方法：重症胰腺炎诊断明确后即经静脉给环丙沙星０．２ｇ加甲硝唑０．５ｇ，每１２小时一次，以后根据病情或药敏试验选用有效治疗性抗菌药物。结果：发生胰腺及胰同感染１１例（１０．３％），均为重症Ⅱ型及ＢａｌｔｈａｚａｒＤ、Ｅ级，细菌种类包括大肠杆菌、肠球菌、假单胞菌属及念珠菌等。肺及泌尿系感染１６例（１％），肠道菌群紊乱及真菌感染２７例（２５．２％）。死亡１２例，死亡率１１．２％。提示对重症急性胰腺炎预防性使用抗菌药物能降低继发胰腺感染的发生率及死亡率。抗菌药物应用时间不宜太长；若伴真菌感染，应给予抗真菌药物。     

遏制轻型急性胰腺炎向重症转化的非手术 治疗策略

目的 ：探讨遏制急性胰腺炎向重症转化的非手术治疗策略。方法 ：将4年间收治的286例轻型急性胰腺炎分为对照组和治疗观察组。对照组采取常规非手术治疗措施;观察组加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗方法。结果 ：对照组144轻型有20例转化为重症胰腺炎，14例发生全身性并发症;观察组142例轻型有8例转化为重症，2例出现全身性并发症。观察组重症患者血C-反应蛋白和Balthazar CT严重度指数在治疗后各时点较对照组明显降低。结论 ：在常规治疗的基础上加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗措施可能有助于阻止轻型急性胰腺炎向重症化发展。     

CT引导下胰腺穿刺早期诊断胰腺感染

作者对１９９０年至１９９６年收治的１２２例重症急性胰腺炎中持续发热、白细胞增高、疑有感染的２１例患者行ＣＴ引导下细针穿刺细菌学检查，确定有无胰腺感染。在ＣＴ引导下根据病变的部位选择适当的穿刺点及进针方向。穿刺点可经前腹壁、侧腹壁或脊柱旁，并对穿刺液行细菌学检查。结果：（１）２１例共穿刺３５例次，无穿刺所致并发症。（２）证实胰腺感染１３例。细菌种类包括大肠杆菌、假单胞菌属及霉菌等；单一细菌感染７例，多种细菌感染６例。（３）胰腺感染者ＣＴ表现均为Ｄ或Ｅ级；除１例感染性假性囊肿发生于发病后３个月外，其他均发生于胰腺炎发病后４～１５天，平均１０．２天。（４）８例穿刺阴性者除１例因应激性溃疡大出血手术外，均经支持治疗治愈。提示ＣＴ引导下胰腺穿刺是早期诊断胰腺感染的可靠方法。     

A Double-blind, Placebo-controlled Trial of Ciprofloxacin Prophylaxis in Patients with Acute Necrotizing Pancreatitis

Background  The use of prophylactic antibiotics in acute severe necrotizing pancreatitis is controversial. Methods  Prospective, randomized, placebo-controlled, double-blind study was carried out at Bellvitge Hospital, in Barcelona, Spain. Among 229 diagnosed with severe acute pancreatitis, 80 had evidence of necrotizing pancreatitis (34/80 patients were excluded of the protocol). Forty-six patients without previous antibiotic treatment with pancreatic necrosis in a contrast-enhanced CT scan were randomly assigned to receive either intravenous ciprofloxacin or placebo. Five patients were secondarily excluded, and the remaining 41 patients were finally included in the study (22 patients received intravenous ciprofloxacin and 19 patients placebo). Results  Comparing the 22 with intravenous ciprofloxacin and 19 with placebo, infected pancreatic necrosis was detected in 36% and 42% respectively (p = 0.7). The mortality rate was 18% and 11%, respectively (p = 0.6). No significant differences between both treatment groups were observed with respect to variables such as: non-pancreatic infections, surgical treatment, timing and the re-operation rate, organ failure, length of hospital and ICU stays. Conclusion  The prophylactic use of ciprofloxacin in patients with severe necrotizing pancreatitis did not significantly reduce the risk of developing pancreatic infection or decrease the mortality rate. The small number of patients included in this study should be considered. This study was promoted by the “Bellvitge Hospital” and has not received any grant or payment from the pharmaceutical industry.     

Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study

BACKGROUND & AIMS: In patients with severe, necrotizing pancreatitis, it is common to administer early, broad-spectrum antibiotics, often a carbapenem, in the hope of reducing the incidence of pancreatic and peripancreatic infections, although the benefits of doing so have not been proved. METHODS: A multicenter, prospective, double-blind, placebo-controlled randomized study set in 32 centers within North America and Europe. Participants: One hundred patients with clinically severe, confirmed necrotizing pancreatitis: 50 received meropenem and 50 received placebo. Interventions: Meropenem (1 g intravenously every 8 hours) or placebo within 5 days of the onset of symptoms for 7 to 21 days. Main Outcome Measures: Primary endpoint: development of pancreatic or peripancreatic infection within 42 days following randomization. Other endpoints: time between onset of pancreatitis and the development of pancreatic or peripancreatic infection; all-cause mortality; requirement for surgical intervention; development of nonpancreatic infections within 42 days following randomization. RESULTS: Pancreatic or peripancreatic infections developed in 18% (9 of 50) of patients in the meropenem group compared with 12% (6 of 50) in the placebo group (P = 0.401). Overall mortality rate was 20% (10 of 50) in the meropenem group and 18% (9 of 50) in the placebo group (P = 0.799). Surgical intervention was required in 26% (13 of 50) and 20% (10 of 50) of the meropenem and placebo groups, respectively (P = 0.476). CONCLUSIONS: This study demonstrated no statistically significant difference between the treatment groups for pancreatic or peripancreatic infection, mortality, or requirement for surgical intervention, and did not support early prophylactic antimicrobial use in patients with severe acute necrotizing pancreatitis.     

Acute necrotizing pancreatitis: treatment strategy according to the status of infection

OBJECTIVE: To determine benefits of conservative versus surgical treatment in patients with necrotizing pancreatitis. SUMMARY BACKGROUND DATA: Infection of pancreatic necrosis is the most important risk factor contributing to death in severe acute pancreatitis, and it is generally accepted that infected pancreatic necrosis should be managed surgically. In contrast, the management of sterile pancreatic necrosis accompanied by organ failure is controversial. Recent clinical experience has provided evidence that conservative management of sterile pancreatic necrosis including early antibiotic administration seems promising. METHODS: A prospective single-center trial evaluated the role of nonsurgical management including early antibiotic treatment in patients with necrotizing pancreatitis. Pancreatic infection, if confirmed by fine-needle aspiration, was considered an indication for surgery, whereas patients without signs of pancreatic infection were treated without surgery. RESULTS: Between January 1994 and June 1999, 204 consecutive patients with acute pancreatitis were recruited. Eighty-six (42%) had necrotizing disease, of whom 57 (66%) had sterile and 29 (34%) infected necrosis. Patients with infected necrosis had more organ failures and a greater extent of necrosis compared with those with sterile necrosis. When early antibiotic treatment was used in all patients with necrotizing pancreatitis (imipenem/cilastatin), the characteristics of pancreatic infection changed to predominantly gram-positive and fungal infections. Fine-needle aspiration showed a sensitivity of 96% for detecting pancreatic infection. The death rate was 1.8% (1/56) in patients with sterile necrosis managed without surgery versus 24% (7/29) in patients with infected necrosis (P <.01). Two patients whose infected necrosis could not be diagnosed in a timely fashion died while receiving nonsurgical treatment. Thus, an intent-to-treat analysis (nonsurgical vs. surgical treatment) revealed a death rate of 5% (3/58) with conservative management versus 21% (6/28) with surgery. CONCLUSIONS: These results support nonsurgical management, including early antibiotic treatment, in patients with sterile pancreatic necrosis. Patients with infected necrosis still represent a high-risk group in severe acute pancreatitis, and for them surgical treatment seems preferable.     

Prophylaxis for septic complications in acute necrotizing pancreatitis

Because the mortality of severe pancreatitis is higher when infected necrosis supervenes, prevention of infections has become a relevant endpoint for management. The "ideal" drug should be characterized by specific activity against the bacteria known to be responsible for infection and should be able to penetrate the gland in a sufficient concentration. To date there have been eight prospective trials with antibiotics, one on selective digestive decontamination, and others with enteral nutrition. A meta-analysis regarding experiences with antimicrobial drugs reports a significant reduction in the incidence of infected necrosis and pancreatic abscesses during severe pancreatitis. In conclusion, among the several options aimed at reducing infections during necrotizing pancreatitis, the prophylactic use of antibacterial drugs is the only one to have been tested to date in several randomized studies. Strong consideration should be given to treating patients with severe pancreatitis with broadspectrum antibiotics, selective digestive decontamination, and enteral nutrition. Received: June 5, 2000 / Accepted: December 28, 2000     

Time course of bacterial infection of the pancreas and its relation to disease severity in a rodent model of acute necrotizing pancreatitis.

BACKGROUND: Bacterial infection of pancreatic necrosis is thought to be a major determinant of outcome in acute necrotizing pancreatitis. The determinants and possibilities for prophylaxis are unknown and difficult to study in humans. OBJECTIVE: The time course of bacterial infection of the pancreas in a rodent model of acute necrotizing pancreatitis was characterized. The authors ascertained if there is a correlation with the degree of necrosis. METHODS: Acute pancreatitis (AP) of graded severity was induced under sterile conditions by an intravenous infusion of cerulein (5 micrograms/kg/hr) for 6 hours (mild AP), or a combination of intravenous cerulein with an intraductal infusion of 10-mM glycodeoxycholic acid (0.2 mL for 2 min for moderate AP, 0.5 mL for 10 min for severe AP). Sham-operated animals (intravenous and intraductal NaCl 0.9%) served as controls. Ninety-six hours after induction, animals were killed for quantitative bacterial examination and histologic scoring of necrosis. In addition, groups of animals with severe AP were investigated at 12, 24, 48, 96, and 144 hours. RESULTS: No significant pancreatic necrosis was found in control animals (0.3 +/- 0.1) or animals with mild AP (0.6 +/- 0.1) killed at 96 hours. Necrosis scores were 1.1 +/- 0.2 for animals with moderate AP and 1.9 +/- 0.2 for animals with severe AP. Control animals did not develop significant bacterial infection of the pancreas (> or = 10(3) CFU/g). At 96 hours, the prevalence of infection was 37.5% in animals with mild AP and 50% in animals with moderate AP. In animals with severe AP, infection of the pancreas increased from 33% in the first 24 hours to 75% between 48 and 96 hours (p < 0.05). The bacterial counts and the number of different species increased with time and was maximal (> 10(11) CFU/g) at 96 hours. CONCLUSION: Bacterial infection of the pancreas in rodent AP increases during the first several days, and its likelihood correlates with the severity of the disease. This model, which closely mimics the features of human acute pancreatitis, provides a unique opportunity to study the pathogenesis of infected necrosis and test therapeutic strategies.     

Frequency and time course of pancreatic and extrapancreatic bacterial infection in experimental acute pancreatitis in rats

BACKGROUND: Infectious complications in severe pancreatitis are the main factors determining clinical course and outcome. The taurocholate model for acute necrotizing pancreatitis was evaluated for frequency and time course of pancreatic and extrapancreatic bacterial infection. METHODS: Sixty-five male Wistar rats were divided into 5 groups of 13 animals each. Specimens for bacteriologic examination were taken, and pancreatitis was induced by intraductal infusion of 3% taurocholate under sterile conditions. Animals were killed 8, 16, 24, or 32 hours thereafter, and bacteriologic examination was performed. A control group of animals with intraductal infusion of 0.9% saline solution were killed after 32 hours. RESULTS: There was no significant pancreatic infection in the control group and in the 8-hour group (1 of 13 rats). Sixteen and 24 hours after induction of pancreatitis, infection and inflammation of the pancreas were found in 77% (10 of 13 rats), and after 32 hours pancreatic infection occurred in 69% (9 of 13 rats). Extrapancreatic bacterial infection after 16 hours occurred in the liver (62%), spleen (62%), and mesenteric lymph nodes (46%). Bacteria infecting the pancreas reflected the bacterial spectrum of the large bowel and terminal ileum before induction of pancreatitis (Escherichia coli [77%], Proteus [43%], Enterococcus [37%], and Staphylococcus [23%]). CONCLUSIONS: Pancreatic infection is an early and frequent finding in the taurocholate model of acute necrotizing pancreatitis. Infection occurs between 8 and 16 hours after induction of pancreatitis. The source of infecting bacteria seems to be the large bowel or the terminal ileum. We present a useful model of severe pancreatitis in which to study bacterial translocation, the further route of spread, and therapeutic approaches.     

CT引导下细针穿刺早期诊断急性坏死性胰腺炎继发感染

目的 探讨应用ＣＴ引导下细针穿刺（ＦＮＡ）早期诊断急性坏死性胰腺炎继发感染的方法。;方法 对１４例临床怀疑有继发感染的急性坏死性胰腺炎患者行ＣＴ引导下ＦＮＡ。抽吸物行涂片革兰染色、细菌培养以及聚合酶链反应（ＰＣＲ）细菌检测。结果 １０例最终诊断为胰腺感染,４例最终诊断为胰腺未感染,共行ＦＮＡ１５例次,其中,１２例次经左侧腹膜后穿刺,１例次同时行左侧和右侧腹膜后穿刺,２例次经腹腔穿刺,与最终诊断结果比较,ＦＮＡ抽吸物涂片、ＰＣＲ、培养诊断胰腺感染的敏感性分别为７／１０、９／１０、１０／１０,特异性均为４／４,需要时间分别为３０ｍｉｎ、４ｈ、３ｄ。结论 对多数急性坏死性胰腺炎患者可选择腹膜后路径行ＣＴ引导下ＦＮＡ,以避开胃肠和重要脏器;抽吸物ＰＣＲ诊断胰腺感染,快速准确,适应临床快速诊断胰腺感染的要求。     

Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg⁻¹/day⁻¹). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN-supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.     

Acute pancreatitis: a prospective study of its incidence, aetiology, severity, and mortality in Iceland.

OBJECTIVE: To evaluate the incidence, aetiology, severity and mortality of patients with acute pancreatitis. DESIGN: Prospective study. SETTING: University hospital, Iceland. PATIENTS AND METHODS: All 50 patients diagnosed with acute pancreatitis during the one-year period October 1998-September 1999 inclusive. MAIN OUTCOME MEASURES: APACHE II, and Ranson and Imrie scores, and C-reactive protein (CRP) concentrations. The Balthazar-Ranson criteria were used for scoring of computed tomograms (CT). RESULTS: 27 of the 50 patients were male. The median age of the whole series was 60 years (range 19-85). The estimated incidence was 32/100000 for the first attack of acute pancreatitis. The causes were; gallstones 21 (42%), alcohol 16 (32%), miscellaneous 12 (24%), and idiopathic 1 (2%). 15 (33%) of the patients had APACHE II scores > or = 9, 17 (38%) had Ranson scores of > or = 3, 23 (50%) had Imrie scores of > or = 3, and 16 (34%) had CRP concentrations over 210 mg/L during the first 4 days or > 120 mg/L during the first week. Seven patients had severe pancreatitis. 2 patients in the whole group died, and both had clinically severe pancreatitis. CONCLUSIONS: This study indicates that the incidence of less severe acute pancreatitis is rising. Prospective assessment makes it possible to evaluate the aetiological factors more accurately. Measurement of the CRP concentration is an attractive and simple alternative to the severity scoring systems currently in use.     

Preoperative versus postoperative endoscopic retrograde cholangiopancreatography in mild to moderate gallstone pancreatitis: a prospective randomized trial

OBJECTIVE: To determine whether endoscopic retrograde cholangiopancreatography (ERCP) and common bile duct (CBD) stone extraction should be performed routinely before surgery or'selectively after surgery in patients with mild to moderate gallstone pancreatitis. SUMMARY BACKGROUND DATA: The role and timing of ERCP in mild to moderate gallstone pancreatitis remains controversial. Routine preoperative ERCP identifies persisting CBD stones but carries risks of complications and may delay definitive care. Selective postoperative ERCP, performed only if a CBD stone is seen on intraoperative cholangiography (IOC), avoids unnecessary ERCP but risks unsuccessful stone extraction. METHODS: A prospective, randomized study of consecutive patients with gallstone pancreatitis was conducted. Using previously determined criteria, patients with acute cholangitis or necrotizing pancreatitis were excluded. Patients considered at high risk for persisting CBD stones (CBD size > or =8 mm on admission ultrasound, serum total bilirubin > or = 1.7 mg/dL, or serum amylase > or = 150 U/L on hospital day 4) were randomly assigned to routine preoperative ERCP followed by laparoscopic cholecystectomy, or laparoscopic cholecystectomy with selective postoperative ERCP and endoscopic sphincterotomy only if a CBD stone was present on IOC. Primary end points were costs, length of hospital stay, and the combined treatment failure rates (failure of diagnostic ERCP and IOC, complications of ERCP and endoscopic sphincterotomy, and complications of surgery). RESULTS: One hundred fifty-four consecutive patients with gallstone pancreatitis were evaluated prospectively for study eligibility. Sixty patients met the randomization criteria. Thirty patients were randomized to routine preoperative ERCP and 29 patients to selective postoperative ERCP (1 patient refused). Age, admission laboratory values, and APACHE II and Imrie scores were similar in both groups. By protocol, ERCP was performed in all patients in the preoperative ERCP group. In the postoperative ERCP group, ERCP was necessary in only 7 of 29 patients (24%). Mean hospital stay was significantly longer in the routine preoperative ERCP group (11.7 days) than in the selective postoperative ERCP group (9.0 days). Mean total cost was higher in the preoperative ERCP group ($9,426) than in the postoperative ERCP group ($7,798). The combined treatment failure rate was 10% in both groups. CONCLUSIONS: In patients with mild to moderate gallstone pancreatitis without cholangitis, selective postoperative ERCP and CBD stone extraction is associated with a shorter hospital stay, less cost, no increase in combined treatment failure rate, and significant reduction in ERCP use compared with routine preoperative ERCP.     

Isovolemic hemodilution with dextran 60 as treatment of pancreatic ischemia in acute pancreatitis. Clinical practicability of an experimental concept.

OBJECTIVE: This phase-I study transferred the concept of isovolemic hemodilution, which has been proven beneficial in the treatment of experimental acute pancreatitis to the patient. SUMMARY BACKGROUND DATA: Pancreatic ischemia represents one main mechanism in the pathogenesis of necrotizing pancreatitis. Isovolemic hemodilution with dextran 60 has been shown experimentally to limit the progression of pancreatic necrosis by improving pancreatic microcirculation. METHODS: Thirteen patients with clinically severe nonbiliary pancreatitis and CT-classification E according to Balthazar were enrolled. Exclusion criteria were anemia, coronary heart disease, chronic obstructive pulmonary disease, coagulopathies, and secondary referral. The volume of blood to be exchanged for dextran 60 was calculated from a nomogram based on body surface. Isovolemic hemodilution aimed at a hematocrit of 30%. Independent from the exchange procedure conventional fluid resuscitation was performed to adjust the central venous pressure at 6 +/- 2 mm Hg. RESULTS: Whole blood (750-1,700 mL) was exchanged for dextran 60 during 45 to 70 minutes. No adverse effect was encountered; central hemodynamics were not affected. Considering a mean Ranson score of 5, mortality was low (7.7%). Progression of pancreatic necrosis was registered in only two patients subsequently undergoing surgical treatment (15%). CONCLUSIONS: Isovolemic hemodilution is practicable in patients. A randomized trial has to prove whether isovolemic hemodilution can substantially alter the course of acute pancreatitis as anticipated from animal studies.     

Late mortality in patients with severe acute pancreatitis.

BACKGROUND: Mortality due to severe or necrotizing acute pancreatitis most often results from multiorgan dysfunction syndrome (MODS) occurring either early (within the first 14 days) or 2 weeks or more after the onset of symptoms due to septic complications. The aim of this study was to analyse the course of the disease in patients who died from severe acute pancreatitis. METHODS: Between January 1994 and August 2000 details of 263 consecutive patients with acute pancreatitis were entered prospectively into a database. All patients were treated in an intermediate or intensive care unit. RESULTS: The overall mortality rate was 4 per cent (ten of 263 patients). The mortality rate was 9 per cent (ten of 106) in patients with necrotizing disease. No patient died within the first 2 weeks of disease onset. The median day of death was 91 (range 15-209). Six patients died from septic MODS. Ranson score, Acute Physiology and Chronic Health Evaluation (APACHE) II score during the first week of disease, pre-existing co-morbidity, body mass index, infection and extent of necrosis were significantly associated with death (P < 0.01 for all parameters). However, only infection of the necrotic pancreas was an independent risk factor in the multivariate analysis. CONCLUSION: Early deaths in patients with severe acute pancreatitis are rare, mainly as a result of modern intensive care treatment. Nine of the ten deaths occurred more than 3 weeks after disease onset. Infection of pancreatic necrosis was the main risk factor for death.     

Early enteral feeding in severe acute pancreatitis: can it prevent secondary pancreatic (super) infection?

Sepsis continues to account for a second peak in mortality in patients with severe acute pancreatitis. The prevention of these septic complications and subsequent development of multiple organ dysfunction syndrome remains a major focus for investigators, yet despite considerable clinical and experimental work addressing its etiology, septic complications remain high. Several studies have been designed to demonstrate the mechanism of origin of these septic complications with an attempt to define strategies for their prevention to improve patient outcomes. There is clear evidence that the origin of this secondary bacterial infection arises from enteric bacterial translocation secondary to disruption of the gut mucosal barrier during acute pancreatitis. Strategies designed to prevent secondary pancreatic infection include aggressive fluid resuscitation to maximize organ perfusion, early systemic antibiotic treatment or selective gut decontamination, and recently attempts to block mediators of the systemic inflammatory response. This discussion will summarize our present understanding of the etiopathogenesis of secondary bacterial 'superinfection' of necrotizing pancreatitis and how the initiation of enteral feeding early in the course of acute pancreatitis may prove to be an effective means of preventing and/or reversing the breakdown of the gut mucosal defense barrier.