Masamune A, Kikuta K, Hamada S, Tsuji I, Takeyama Y, Shimosegawa T, Okazaki K; Japan Pancreas Society.
Clinical practice of acute pancreatitis in Japan: An analysis of nationwide epidemiological survey in 2016.
Pancreatology. 2020 Jun;20(4):629-636. doi: 10.1016/j.pan.2020.04.013. Epub 2020 May 1.
Abstract/Text
BACKGROUND: To provide updates on clinical practice of acute pancreatitis (AP) in Japan, we conducted a nationwide epidemiological survey.
METHODS: This study consisted of a two-staged survey; the number of AP patients was estimated by the first-stage survey and their clinical features were examined by the second-stage survey. We surveyed AP patients who had visited hospitals in 2016.
RESULTS: The estimated number of AP patients in 2016 was 78,450, with an overall incidence of 61.8 per 100,000 persons. We obtained detailed clinical information of 2994 AP patients, including 706 (23.6%) severe cases classified according to the Japanese severity criteria. The male-to-female sex ratio was 2.0, and the mean age at onset was 59.9 years in males and 66.5 years in females. Alcohol was the most common etiology (42.8%) in males and gallstones in females (37.7%). The AP-associated mortality was 6.1% in severe AP cases, which was decreased by 40% compared to the 2011 survey. Antibiotics were administered to most cases, with carbapenem being frequently used. Enteral nutrition was given in 31.8% of severe cases, but majority cases received after 48 h. Among the 107 patients who received intervention for walled-off necrosis, five patients received surgery-first approach, 66 received endoscopic ultrasound-guided transluminal drainage, and 19 underwent step-up approach.
CONCLUSIONS: We clarified the current status of AP in Japan including the significant reduction of mortality in severe cases, shift to endoscopic approaches for walled-off necrosis, and poor compliance of the recommendations in the guidelines including management of enteral nutrition and antibiotic administration.
Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.
急性膵炎診療ガイドライン2021改訂出版委員会 編：急性膵炎診療ガイドライン 2021年 第5版、金原出版、2021.
Forsmark CE, Baillie J; AGA Institute Clinical Practice and Economics Committee; AGA Institute Governing Board.
AGA Institute technical review on acute pancreatitis.
Gastroenterology. 2007 May;132(5):2022-44. doi: 10.1053/j.gastro.2007.03.065.
Abstract/Text
Yang AL, Vadhavkar S, Singh G, Omary MB.
Epidemiology of alcohol-related liver and pancreatic disease in the United States.
Arch Intern Med. 2008 Mar 24;168(6):649-56. doi: 10.1001/archinte.168.6.649.
Abstract/Text
BACKGROUND: The epidemiology of acute alcoholic pancreatitis (AP), chronic alcoholic pancreatitis (CP), acute alcoholic hepatitis (AH), and chronic alcoholic hepatitis with cirrhosis (CH) alone or in combination is not well described. To better understand alcohol-related liver and pancreas effects on and associations with different ethnic groups and sexes, we analyzed the trends of AP, CP, AH, CH, AP plus AH, and CP plus CH in the United States.
METHODS: We examined discharge records from the Nationwide Inpatient Sample, the largest representative sample of US hospitals. Hospital discharges, case-fatality, and sex and race contributions were calculated from patients with discharge diagnoses of AP, CP, AH, CH, AP plus AH, or CP plus CH between 1988 and 2004.
RESULTS: The distribution of overall hospital discharges per 100 000 persons between 1988 and 2004 was as follows: AP, 49.2; CP, 8.1; AH, 4.5; and CH, 13.7. Overall hospital discharges per 100 000 persons for AP plus AH were 1.8; and for CP plus CH, 0.32. There were higher male to female ratios for AH and CH, and less so for AP and CP. A markedly higher frequency of AP (63.5) and CP (11.3) was seen among blacks than among whites (AP, 29.6 and CP, 5.1), Hispanics (AP, 27.1 and CP, 3.7), Asians (AP, 12.8 and CP, 1.4), and American Indians (AP, 15.5 and CP, 2.3). This higher frequency remained stable between 1994 and 2004. Overall case fatality steadily decreased in all categories, but remains highest in CH (13.6%) with similar racial distributions.
CONCLUSIONS: In the United States, AP is the most common discharge diagnosis among alcohol-related liver or pancreas complications, while CH has the highest case fatality rate and male to female ratio. Blacks have the highest frequency of alcohol-related pancreatic disease.
Fortson MR, Freedman SN, Webster PD 3rd.
Clinical assessment of hyperlipidemic pancreatitis.
Am J Gastroenterol. 1995 Dec;90(12):2134-9.
Abstract/Text
OBJECTIVE: This study addresses three questions: 1) What are the clinical presentations of pancreatitis secondary to hyperlipidemia? 2) What is the role of alcohol, diabetes, or known causes of hypertriglyceridemia? and 3) Does the course of pancreatitis secondary to hypertriglyceridemia differ from that of other etiologies?
METHODS: We reviewed patients between 1982 and 1994 with a diagnosis of pancreatitis (577.0) and hypertriglyceridemia (272.0). Four hospitals participated. Seventy patients had a clinical presentation consistent with pancreatitis, that is elevated amylase and lipase or evidence of pancreatitis by ultrasound or CT imaging and serum triglyceride levels greater than 500 mg/dl or lactescent serum. Clinical data were derived from hospital admissions.
RESULTS: Hypertriglyceridemia was the etiology in 1.3-3.8% of patients discharged with a diagnosis of pancreatitis. A history of diabetes mellitus was present in 72%, hypertriglyceridemia in 77%, alcohol use 23%, and gallstones in 7%. Lipemic serum was described on admission in 45%. Mean triglyceride levels were 4587 +/- 3616 ml/dl. Amylase was elevated two times normal in 54%, and lipase was elevated two times normal in 67%. CT scans were abnormal in 82%, with peripancreatic fluid in 34%, pseudocyst 37%, and necrosis in 15%. Abscess occurred in 13%, death in 6%.
CONCLUSION: Acute pancreatitis secondary to hyperlipidemia is characterized by three presentations. All patients present with abdominal pain, nausea, and vomiting of hours to days duration. The most common presentation is a poorly controlled diabetic with a history of hypertriglyceridemia. The second presentation is the alcoholic found to have hypertriglyceridemia or lactescent serum on admission. The third, about 15-20% of patients, is the nondiabetic, nonalcoholic, nonobese patient with drug- or diet-induced hypertriglyceridemia.
Scherer J, Singh VP, Pitchumoni CS, Yadav D.
Issues in hypertriglyceridemic pancreatitis: an update.
J Clin Gastroenterol. 2014 Mar;48(3):195-203. doi: 10.1097/01.mcg.0000436438.60145.5a.
Abstract/Text
Hypertriglyceridemia (HTG) is a well-established but underestimated cause of acute pancreatitis and recurrent acute pancreatitis. The clinical presentation of HTG-induced pancreatitis (HTG pancreatitis) is similar to other causes. Pancreatitis secondary to HTG is typically seen in the presence of one or more secondary factors (uncontrolled diabetes, alcoholism, medications, pregnancy) in a patient with an underlying common genetic abnormality of lipoprotein metabolism (familial combined hyperlipidemia or familial HTG). Less commonly, a patient with rare genetic abnormality (familial chylomicronemic syndrome) with or without an additional secondary factor is encountered. The risk of acute pancreatitis in patients with serum triglycerides >1000 and >2000 mg/dL is ∼ 5% and 10% to 20%, respectively. It is not clear whether HTG pancreatitis is more severe than when it is due to other causes. Clinical management of HTG pancreatitis is similar to that of other causes. Insulin infusion in diabetic patients with HTG can rapidly reduce triglyceride (TG) levels. Use of apheresis is still experimental and better designed studies are needed to clarify its role in the management of HTG pancreatitis. Diet, lifestyle changes, and control of secondary factors are key to the treatment, and medications are useful adjuncts to the long-term management of TG levels. Control of TG levels to 500 mg/dL or less can effectively prevent recurrences of pancreatitis.
Rünzi M, Layer P.
Drug-associated pancreatitis: facts and fiction.
Pancreas. 1996 Jul;13(1):100-9. doi: 10.1097/00006676-199607000-00014.
Abstract/Text
In the past, numerous reports on drugs probably causing acute pancreatitis have been published. However, most of these case reports were anecdotal with a lack of obvious evidence and did not present a comprehensive summary. Although drug-associated pancreatitis is rare, it is gaining increasing importance with the introduction of several potent new agents, i.e., anti-acquired immunodeficiency syndrome drugs. The following comprehensive review scrutinizes the evidence present in the world literature on drugs associated with acute or chronic pancreatitis and, based on this, categorizes in a definite, probable, or possible causality. In addition, explanations for the pathophysiological mechanisms are discussed.
Wilmink T, Frick TW.
Drug-induced pancreatitis.
Drug Saf. 1996 Jun;14(6):406-23. doi: 10.2165/00002018-199614060-00006.
Abstract/Text
Few data exist about the incidence of drug-induced pancreatitis in the general population. 20 cases of drug-related pancreatitis were reported in Switzerland over a period of 12 years. The proportion of cases of pancreatitis caused by drugs is estimated to be around 2% in the general population, with much higher proportions in specific subpopulations, such as children and patients who are HIV positive. The literature about drug-induced pancreatitis consists mainly of anecdotal case reports. Clear evidence of a definite association with pancreatitis, by means of rechallenge tests, or consistent case reports, supported by animal experiments or data on the incidence of acute pancreatitis in drug trials exists for didanosine, valproic acid (sodium valproate), aminosalicylates, estrogen, calcium, anticholinesterases and sodium stibogluconate. An association with drug-induced pancreatitis is likely but not definitely proven for thiazide diuretics, pentamidine, ACE inhibitors, asparaginase, vinca alkaloids, some nonsteroidal anti-inflammatory drugs and clozapine. Pancreatitis is possibly caused by azathioprine, furosemide (frusemide), tetracycline, metronidazole, isoniazid, rifampicin (rifampin), sulphonamides, cyclosporin and some antineoplastic drugs. Many drugs have been reported to be associated with acute pancreatitis. However, lack of rechallenge evidence, consistent statistical data, or evidence from experimental studies on a possible mechanism prohibit definitive conclusions about most of them. The high incidence of concurrent illnesses known to induce acute pancreatitis, makes a trigger role or co-factor role for the drug seem most likely.
McArthur KE.
Review article: drug-induced pancreatitis.
Aliment Pharmacol Ther. 1996 Feb;10(1):23-38. doi: 10.1111/j.1365-2036.1996.tb00174.x.
Abstract/Text
Drugs are a relatively uncommon cause of pancreatitis in adult patients, but should be considered when other reasonable causes of pancreatitis are not present. A wide variety of drugs have been reported to cause pancreatitis. Drug-induced pancreatitis is almost always acute and may be mild to fatal in severity. Definite proof that a drug causes pancreatitis requires that pancreatitis develops during treatment with the drug, that other likely causes of pancreatitis are not present, that pancreatitis resolves upon discontinuing the drug, and that pancreatitis usually recurs upon readministration of the drug. For ethical reasons, rechallenge with the suspect drug can be done only if the drug is necessary to treat a serious condition; thus this highly convincing piece of evidence relating the drug to pancreatitis may not be available. Information about drug-related pancreatitis is often not readily available, particularly for newer drugs. Clinicians should consider obtaining information directly from regulatory agencies and manufacturers as well as the literature.
Spanier BW, Tuynman HA, van der Hulst RW, Dijkgraaf MG, Bruno MJ.
Acute pancreatitis and concomitant use of pancreatitis-associated drugs.
Am J Gastroenterol. 2011 Dec;106(12):2183-8. doi: 10.1038/ajg.2011.303. Epub 2011 Sep 13.
Abstract/Text
OBJECTIVES: Drug-induced pancreatitis (DIP) is considered a relative rare disease entity, perhaps due to lack of recognition. The objective of this study was to evaluate the prevalence of pancreatitis-associated drugs in a Dutch cohort of patients admitted for acute pancreatitis (AP) and to identify the proportion AP possibly attributable to the use of drugs.
METHODS: This was a multicenter observational study (EARL study). Etiology, disease course, use of pancreatitis-associated drugs at hospital admittance, and discontinuation of these drugs were evaluated. Drugs were scored by means of an evidence-based DIP classification system.
RESULTS: The first documented hospital admissions of 168 patients were analyzed. In all, 70 out of 168 (41.6%; 95% confidence interval (CI): 34.5-49.2%) patients used pancreatitis-associated drugs at admission. In 26.2% (44/168; 95% CI: 20.1-33.3%) of cases, at least one class I pancreatitis-associated drug was used. Possibly DIP was present in 12.5% (21/168; 95% CI: 8.3-18.4%); in less than half of these patients (9/21 or 42.9%; 95% CI: 24.5-63.5%), the prescribed drugs were actually discontinued, with no recurrence of AP later on. Among the remaining 12 patients without discontinuation of their drugs use and in absence of an alternative etiologic cause of AP, 8 patients used a class I pancreatitis-associated drug, representing 4.8% (8/168, 95% CI: 2.4-9.1%) of the total study population.
CONCLUSIONS: In this series, a remarkably high percentage of patients who were admitted because of an attack of AP used pancreatitis-associated drugs. Physicians should be more aware of the possibility of DIP in patients with otherwise unexplained AP and act appropriately by discontinuation of the drug.
Moreau JA, Zinsmeister AR, Melton LJ 3rd, DiMagno EP.
Gallstone pancreatitis and the effect of cholecystectomy: a population-based cohort study.
Mayo Clin Proc. 1988 May;63(5):466-73. doi: 10.1016/s0025-6196(12)65644-4.
Abstract/Text
Although an association between gallstones and pancreatitis has been recognized for almost 100 years, the risk of acute pancreatitis in patients with gallstones and the effect of cholecystectomy on this risk have been unknown. The complete medical records of the 2,583 residents of Rochester, Minnesota, who had gallstones diagnosed between 1950 and 1970 were carefully reviewed to detect the development of acute pancreatitis. Acute pancreatitis developed in only 89 subjects (3.4% of the cohort); however, the relative risk for acute pancreatitis (before cholecystectomy) was increased 14 to 35 times in men and 12 to 25 times in women. The overall age- and sex-adjusted incidence of acute pancreatitis of the members of the cohort before cholecystectomy was 6.3 to 14.8 per 1,000 person-years of follow-up. Cholecystectomy in 1,560 patients without a prior attack of pancreatitis reduced the relative risk to 1.9 and 2.0 for men and women respectively. Of 58 patients who had a cholecystectomy after an attack of acute pancreatitis and underwent follow-up for a median of 15 years postoperatively, only 2 had another attack of acute pancreatitis, and the cause of the pancreatitis was unrelated to gallstones in both. In summary, patients with gallstones have a considerably increased relative risk for acute pancreatitis and, regardless of whether prior attacks of pancreatitis have occurred, cholecystectomy reduces this risk to almost the same level as in the general population. Because the overall incidence of pancreatitis is low, however, performance of cholecystectomy to prevent pancreatitis is indicated only if an attack of acute pancreatitis has already occurred.
Sankaran SJ, Xiao AY, Wu LM, Windsor JA, Forsmark CE, Petrov MS.
Frequency of progression from acute to chronic pancreatitis and risk factors: a meta-analysis.
Gastroenterology. 2015 Nov;149(6):1490-1500.e1. doi: 10.1053/j.gastro.2015.07.066. Epub 2015 Aug 20.
Abstract/Text
BACKGROUND & AIM: Acute pancreatitis (AP) and chronic pancreatitis (CP) traditionally have been thought to be distinct diseases, but there is evidence that AP can progress to CP. Little is known about the mechanisms of pancreatitis progression. We performed a meta-analysis to quantify the frequency of transition of AP to CP and identify risk factors for progression.
METHODS: We searched PubMed, Scopus, and Embase for studies of patients with AP who developed CP, published from 1966 through November 2014. Pooled prevalence and 95% confidence intervals (CIs) were calculated for these outcomes, and sensitivity, subgroup, and meta-regression analyses were conducted.
RESULTS: We analyzed 14 studies, which included a total of 8492 patients. The pooled prevalence of recurrent AP was 22% (95% CI, 18%-26%), and the pooled prevalence of CP was 10% (95% CI, 6%-15%). Sensitivity analyses yielded a pooled prevalence of CP of 10% (95% CI, 4%-19%) and 36% (95% CI, 20%-53%) in patients after the first occurrence and recurrent AP, respectively. Subgroup analyses found alcohol use and smoking to be the largest risk factors for the development of CP, with pooled prevalence values of 65% (95% CI, 48%-56%) and 61% (95% CI, 47%-73%), respectively. Meta-regression analysis found that men were more likely than women to transition from AP to CP.
CONCLUSIONS: Ten percent of patients with a first episode of AP and 36% of patients with recurrent AP develop CP; the risk is higher among smokers, alcoholics, and men. Prospective clinical studies are needed to study pancreatitis progression.
Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.
Aoun E, Chen J, Reighard D, Gleeson FC, Whitcomb DC, Papachristou GI.
Diagnostic accuracy of interleukin-6 and interleukin-8 in predicting severe acute pancreatitis: a meta-analysis.
Pancreatology. 2009;9(6):777-85. doi: 10.1159/000214191. Epub 2010 Jan 21.
Abstract/Text
OBJECTIVES: The early identification of patients at risk for severe acute pancreatitis (SAP) is crucial. Serum markers of disease severity have been assessed including interleukin (IL)-6 and IL-8; however, their predictive accuracy has varied significantly across studies. We conducted a meta-analysis to assess the accuracy of IL-6 and IL-8 at predicting SAP.
METHODS: We identified relevant published articles and calculated pooled sensitivities, specificities and likelihood ratios using the random-effect model. We included values for days 1, 2 and 3 of presentation for IL-6 and for days 1 and 2 for IL-8. We also constructed summary receiver-operating curves and assessed the area under the curve (AUC) and the diagnostic odds ratios (DORs) as measures of diagnostic accuracy.
RESULTS: For IL-6, we included 7 reports for day 1 and 4 reports for days 2 and 3. For IL-8, we analyzed 5 studies for day 1 and 4 for day 2. The pooled IL-6 sensitivities ranged between 81.0 and 83.6% and specificities between 75.6 and 85.3% with positive likelihood ratios of 3.43, 4.90 and 4.40 for days 1, 2 and 3, respectively. The IL-8 pooled sensitivities were 65.8 and 70.9% with specificities of 66.5 and 91.3% for days 1 and 2 with positive likelihood ratios of 1.96 and 8.15. The IL-6 AUCs were 0.75, 0.88 and 0.85 for days 1, 2 and 3. The IL-8 AUCs were 0.73 and 0.91 for days 1 and 2. The DOR for IL-6 was higher than that of IL-8 on day 1.
CONCLUSION: IL-6 and IL-8 seem to perform at an acceptable level in predicting SAP. Larger confirmatory studies formally comparing this performance with that of more commonly used markers are needed.
Copyright 2010 S. Karger AG, Basel.
Zhang J, Niu J, Yang J.
Interleukin-6, interleukin-8 and interleukin-10 in estimating the severity of acute pancreatitis: an updated meta-analysis.
Hepatogastroenterology. 2014 Jan-Feb;61(129):215-20.
Abstract/Text
BACKGROUND/AIMS: Early identification of severe AP can decrease the mortality rate and complications of SAP. The performance of IL-6 and IL-8 and IL-10 can act as markers of the severity of acute pancreatitis. Therefore, we aimed to evaluate the accuracy of IL-6, IL-8 and IL-10 in estimating the severity of acute pancreatitis.
METHODOLOGY: MEDLINE and PubMed were searched from Jan 1990 to Nov 2012 for relevant studies. We calculated pooled sensitivities and specificities using the Dersimonian-Laird random-effect methods and generate the summary receiver operating curve and area under the curve was reported.
RESULTS: Twelve studies were eligible; 9 reports including 462 patients assessed the accuracy of IL-6 on day 1 of hospital admission, 5 reports including 208 patients on day 2, and 5 reports including 188 patients on day 3. Five studies (n = 299 patients) assessed the accuracy of IL-8 on day 1, and 4 (n = 182 patients) on day 2. They are 4 studies including 284 patients of IL-10 on day 1.
CONCLUSIONS: IL-6, IL-8, and IL-10 may be the predictive markers of SAP. But the best cut-off values and the controversial results of different research may be the largest problem. Therefore, multi-center research and large samples should be done to solve the present problem.
van den Berg FF, de Bruijn AC, van Santvoort HC, Issa Y, Boermeester MA.
Early laboratory biomarkers for severity in acute pancreatitis; A systematic review and meta-analysis.
Pancreatology. 2020 Oct;20(7):1302-1311. doi: 10.1016/j.pan.2020.09.007. Epub 2020 Sep 8.
Abstract/Text
BACKGROUND/OBJECTIVES: Acute pancreatitis is complicated by local and systemic complications in 20-30% of the patients. Accurate prediction of severity may be important for clinical decision making. Our aim is to identify and compare the accuracy of laboratory biomarkers that predict severity and complications in adult patients.
METHODS: Medline, EMBASE, Web of Science and Cochrane Library (1993 to August 2020) were searched for studies with an unselected population of patients with acute pancreatitis, that contains accuracy data for ≥1 laboratory biomarker(s) and/or APACHE-II score for the prediction of a patient outcomes of interest during the first 48 h of admission. The primary outcome is moderate severe or severe acute pancreatitis (MSAP/SAP). Secondary outcomes are severe acute pancreatitis, pancreatic necrosis and organ failure. Risk of bias was assed using QUADAS-2. Biomarkers extracted from ≥3 unique sources, were analyzed using hierarchical summary receiver operating characteristic (HSROC) and bivariate model analysis.
RESULTS: In total, 181 studies were included in the qualitative analysis reporting on 29 biomarkers. For the primary outcome at admission, summary sensitivities and specificities were, respectively, 87% (95% CI 69-95%) and 88% (95% CI 80-93%) for IL-6 at a threshold of >50 pg/ml, 72% (95% CI 64-79%) and 76% (95% CI 67-84%) for an APACHE-II score of ≥8, and 53% (95% CI 35-71%) and 82% (95% CI 74-88%) for CRP >150 mg/l. HSROC curve analysis confirmed these results.
CONCLUSION: This study indicates superiority of IL-6 for the early prediction of MSAP/SAP and may be used for to guide clinical decision making.
Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Funnell IC, Bornman PC, Weakley SP, Terblanche J, Marks IN.
Obesity: an important prognostic factor in acute pancreatitis.
Br J Surg. 1993 Apr;80(4):484-6. doi: 10.1002/bjs.1800800426.
Abstract/Text
Ninety-nine patients with acute pancreatitis in whom body mass index (BMI = weight (kg)/height2 (m2)) was measured were studied prospectively to determine the importance of obesity as a prognostic factor in this disease. Of 19 obese patients (BMI > or = 30 kg/m2), 12 developed severe pancreatitis; seven had abscesses, of whom five died, and two further patients died. In 80 non-obese patients, the incidence of severe pancreatitis (n = 5), abscess formation (n = 4) and death (n = 4) was significantly less (P = 0.0007). The mean(s.d.) BMI of 17 patients with severe acute pancreatitis was significantly higher than that in 82 patients with mild acute disease (31.2(5.6) versus 23.3(5.6) kg/m2, P < 0.001). As a single prognostic factor, obesity had a sensitivity of 63 per cent and a specificity of 95 per cent for predicting disease severity. When five obese women with gallstone pancreatitis were excluded, the sensitivity of obesity increased to 86 per cent. Severe pancreatitis occurred in all eight obese patients with disease of an alcoholic aetiology. These data suggest that increased fat deposits in the peripancreatic and retroperitoneal spaces in obese patients may increase the risk of peripancreatic fat necrosis, abscess and death. Consideration should be given to including obesity as a prognostic factor in acute pancreatitis.
Martínez J, Sánchez-Payá J, Palazón JM, Aparicio JR, Picó A, Pérez-Mateo M.
Obesity: a prognostic factor of severity in acute pancreatitis.
Pancreas. 1999 Jul;19(1):15-20.
Abstract/Text
This study was conducted to assess the prognostic value of obesity in acute pancreatitis and to determine the role played by obesity-associated diseases in the course of the disease. We prospectively studied 49 patients with acute pancreatitis who were divided into three groups according to their body mass index (BMI). There were 22 patients in group I (BMI < or = 25 kg/m2, normal or low weight); 15 in group II (BMI >25 and < or = 29 kg/m2, overweight); and 12 in group III (BMI >29 kg/m2, obese). Other anthropometric parameters also were measured. The severity of pancreatitis was assessed according to the Atlanta classification system. Systemic complications were significantly more common among obese than nonobese patients (p < 0.05). Patients with severe pancreatitis had a higher body-fat percentage, measured by the subscapular skin-fold thickness, and a larger abdominal circumference than patients with mild pancreatitis. Although hypertensive or diabetic patients developed more systemic complications, the multivariate analysis demonstrated that the presence of these underlying diseases did not modify the prognostic role of obesity in acute pancreatitis. We conclude that obesity is a prognostic factor of outcome in acute pancreatitis. Obesity-associated diseases do not vary the prognostic value of obesity. It seems that truncal adiposity is the kind of obesity related to worse outcome of acute pancreatitis.
Tsai CJ.
Is obesity a significant prognostic factor in acute pancreatitis?
Dig Dis Sci. 1998 Oct;43(10):2251-4. doi: 10.1023/a:1026666622394.
Abstract/Text
The role of obesity in acute pancreatitis has not been fully investigated. Based on the new internationally recognized classification system for acute pancreatitis since 1993, the aim of the present study is to evaluate the implications of obesity as an early prognostic indicator for the development of complications in the course of acute pancreatitis. Three hundred twenty patients with acute pancreatitis were consecutively evaluated in a prospective cohort study. Severe acute pancreatitis was defined by the development of organ failure and/or local complications. Obesity was evaluated by measurement of body mass index. The body mass index did not differ significantly between the patients who lived or died (P = 0.51). The obese (body mass index > or =30 kg/m2) had a higher incidence of developing local complications than the nonobese (P < 0.0001). There was no statistical difference in the incidence of developing systemic complications (P = 0.21) or in the mortality (P = 1.0) between the obese and nonobese. These data demonstrated that obese patients had a higher risk of developing local complications in the course of acute pancreatitis. Obesity did not carry an increased risk of developing organ failure or fatal outcome.
Porter KA, Banks PA.
Obesity as a predictor of severity in acute pancreatitis.
Int J Pancreatol. 1991 Nov-Dec;10(3-4):247-52. doi: 10.1007/BF02924162.
Abstract/Text
In order to determine whether the presence of obesity, defined as increased body mass index, would serve as a predictor of severity in acute pancreatitis, we have reviewed the medical records of 27 patients with severe acute pancreatitis. All patients had at least four positive Ranson's signs; all but three patients had at least five Ranson's signs. When the 13 patients with a fatal outcome were compared with the 14 who lived, neither obesity nor respiratory failure was an independent predictor of death. However, when the 27 patients were analyzed on the basis of whether they were obese (15 patients) or not obese (12 patients), obesity was an independent predictor of respiratory failure. Obesity was not a predictor of renal failure, pancreatic necrosis, or need for surgery. We suggest that obese patients with severe acute pancreatitis require close monitoring for the development of respiratory failure.
広田昌彦, 小川道雄: 肥満と急性膵炎(Obesity in acute pancreatitis)．肝胆膵2001; 42: 53-56.
Yeung YP, Lam BY, Yip AW.
APACHE system is better than Ranson system in the prediction of severity of acute pancreatitis.
Hepatobiliary Pancreat Dis Int. 2006 May;5(2):294-9.
Abstract/Text
BACKGROUND: It has been suggested that addition of obesity score to the APACHE-II system can lead to more accurate prediction of severity of acute pancreatitis. However there is scanty information on the usefulness of the combined APACHE-O scoring system in Asian patients. This study aimed to compare the accuracy of Ranson, APACHE-II and APACHE-O systems in assessing severity of acute pancreatitis in a local Chinese population.
METHODS: One hundred and one consecutive patients with acute pancreatitis were prospectively studied. Body mass index (BMI) was measured on admission. Ranson score, APACHE-II and APACHE-O scores were recorded on admission and at 48 hours. By adopting the cut-off levels and definitions advocated in the Atlanta consensus for severe disease, the diagnostic accuracy of the three scoring systems was compared by the area under the curve (AUC) under the receiver operator characteristic curve.
RESULTS: Of the 101 patients, 12 (11.9%) patients suffered from severe pancreatitis. Obesity was uncommon and only two patients (2.0%) had BMI>30. Eighty-two (81.2%) patients were normal weight (BMI< or =25) whereas 17 (16.8%) were overweight (BMI 25-30). Overweight or obesity (BMI>25) was not associated with severe pancreatitis (P=0.40). The AUC for admission scores of Ranson, APACHE-II, and APACHE-O systems was 0.549, 0.904 and 0.904, respectively. The AUC for 48-hour scores of Ranson, APACHE-II and APACHE-O systems was 0.808, 0.955 and 0.951, respectively.
CONCLUSIONS: The APACHE-II scoring system is more accurate than the Ranson scoring system of the prediction of severity in acute pancreatitis. Addition of obesity score does not significantly improve the predictive accuracy of the APACHE-II system in our local population with a low prevalence of obesity.
Dervenis C, Johnson CD, Bassi C, Bradley E, Imrie CW, McMahon MJ, Modlin I.
Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini consensus conference.
Int J Pancreatol. 1999 Jun;25(3):195-210. doi: 10.1007/BF02925968.
Abstract/Text
BACKGROUND: The diagnosis, early assessment, and management of severe acute pancreatitis remain difficult clinical problems. This article presents the consensus obtained at a meeting convened to consider the evidence in these areas. The aim of the article is to provide outcome statements to guide clinical practice, with an assessment of the supporting evidence for each statement.
METHOD: Working groups considered the published evidence in the areas of diagnosis, assessment of severity, nonoperative treatment, and surgical treatment of severe acute pancreatitis. Outcome statements were defined to summarize the conclusions on each point considered. The findings were discussed and agreed on by all participants. A careful assessment was made of the strength of the available evidence (proven, probable, possible, unproven, or inappropriate).
FINDINGS AND CONCLUSIONS: There is reliable evidence to support much current practice. Clear guidance can be given in most areas examined, and several areas were identified where further investigation would be helpful. Diagnosis using plasma concentrations of pancreatic enzymes is reliable. Rapid advances are taking place in the assessment of severity. Several new therapeutic strategies show real promise for the reduction of morbidity and mortality rates. Surgical debridement is required for infected pancreatic necrosis, but is less often necessary for sterile necrosis.
Larvin M, McMahon MJ.
APACHE-II score for assessment and monitoring of acute pancreatitis.
Lancet. 1989 Jul 22;2(8656):201-5. doi: 10.1016/s0140-6736(89)90381-4.
Abstract/Text
The value of the Acute Physiology and Chronic Health Enquiry (APACHE-II) score, the Simplified Acute Physiology score, and the Medical Research Council (MRC) sepsis score were compared with clinical assessment and Ranson and Imrie scores in the evaluation and monitoring of acute pancreatitis in 290 attacks. Attacks were graded mild (231) if uncomplicated, or severe (59) when major organ failure or a pancreatic collection occurred. Only APACHE-II scores were available at the time of admission; they correctly predicted outcome in 77% of attacks and identified 63% of severe attacks, compared with 44% achieved by clinical assessment. After 48 h, APACHE-II was most accurate, and correctly predicted outcome in 88% of attacks, compared with 69% for Ranson and 84% for Imrie scores. APACHE-II predicted 73% of pancreatic collections at 48 h, compared with 65% for Ranson and 58% for Imrie scores. In acute pancreatitis, APACHE-II may facilitate rapid selection of patients for intensive therapy or clinical trials, improve comparison between groups of patients, and indicate that a pancreatic collection is probable.
Hirota M, Mayumi T, Shimosegawa T.
Acute pancreatitis bundles: 10 clinical regulations for the early management of patients with severe acute pancreatitis in Japan.
J Hepatobiliary Pancreat Sci. 2014 Nov;21(11):829-30. doi: 10.1002/jhbp.163. Epub 2014 Sep 11.
Abstract/Text
Masamune A, Hamada S, Kikuta K.
Implementation of Pancreatitis Bundles Is Associated With Reduced Mortality in Patients With Severe Acute Pancreatitis in Japan.
Pancreas. 2021 Feb 1;50(2):e24-e25. doi: 10.1097/MPA.0000000000001750.
Abstract/Text
北野光秀, 吉井宏, 奥沢星二郎, 他: 急性膵炎発症早期の循環動態の変動に関する臨床的研究. 日外会誌1993;94: 824-831.
Mao EQ, Tang YQ, Fei J, Qin S, Wu J, Li L, Min D, Zhang SD.
Fluid therapy for severe acute pancreatitis in acute response stage.
Chin Med J (Engl). 2009 Jan 20;122(2):169-73.
Abstract/Text
BACKGROUND: Fluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP.
METHODS: Seventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group (Group I, n = 36) and a controlled fluid expansion group (Group II, n = 40). Hemodynamic disorders were either quickly (fluid infusion rate was 10 - 15 ml x kg(-1) x h(-1), Group I) or gradually improved (fluid infusion rate was 5 - 10 ml x kg(-1) x h(-1), Group II) through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome (ACS), sepsis, and survival rate were obtained.
RESULTS: The two groups had statistically different (P < 0.05) time intervals to meet fluid expansion criteria (Group I, 13.5 +/- 6.6 hours; Group II, (24.0 +/- 5.4) hours). Blood lactate concentrations were both remarkably lower as compared to the level upon admission (P < 0.05) and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I (35.6% +/- 6.8%) than in Group II (38.5% +/- 5.4%) (P < 0.01). Amount of crystalloid and colloid in group I ((4028 +/- 1980) ml and (1336 +/- 816) ml) on admission day was more than those of group II ((2472 +/- 1871) ml and (970 +/- 633) ml). No significant difference was found in the total amount of fluids within four days of admission between the two groups (P > 0.05). Total amount of fluid sequestration within 4 days was higher in Group I ((5378 +/- 2751) ml) than in Group II ((4215 +/- 1998) ml, P < 0.05). APACHE II scores were higher in Group I on days 1, 2, and 3 (P < 0.05). Rate of mechanical ventilation was higher in group I (94.4%) than in group II (65%, P < 0.05). The incidences of abdominal compartment syndrome (ACS) and sepsis were significantly lower in Group II (P < 0.05). Survival rate was remarkably lower in Group I (69.4%) than in Group II (90%, P < 0.05).
CONCLUSIONS: Controlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset.
Singh VK, Gardner TB, Papachristou GI, Rey-Riveiro M, Faghih M, Koutroumpakis E, Afghani E, Acevedo-Piedra NG, Seth N, Sinha A, Quesada-Vázquez N, Moya-Hoyo N, Sánchez-Marin C, Martínez J, Lluís F, Whitcomb DC, Zapater P, de-Madaria E.
An international multicenter study of early intravenous fluid administration and outcome in acute pancreatitis.
United European Gastroenterol J. 2017 Jun;5(4):491-498. doi: 10.1177/2050640616671077. Epub 2016 Sep 20.
Abstract/Text
AIMS: Early aggressive fluid resuscitation in acute pancreatitis is frequently recommended but its benefits remain unproven. The aim of this study was to determine the outcomes associated with early fluid volume administration in the emergency room (FVER) in patients with acute pancreatitis.
METHODS: A four-center retrospective cohort study of 1010 patients with acute pancreatitis was conducted. FVER was defined as any fluid administered from the time of arrival to the emergency room to 4 h after diagnosis of acute pancreatitis, and was divided into tertiles: nonaggressive (<500 ml), moderate (500 to 1000 ml), and aggressive (>1000 ml).
RESULTS: Two hundred sixty-nine (26.6%), 427 (42.3%), and 314 (31.1%) patients received nonaggressive, moderate, and aggressive FVER respectively. Compared with the nonaggressive fluid group, the moderate group was associated with lower rates of local complications in univariable analysis, and interventions, both in univariable and multivariable analysis (adjusted odds ratio (95% confidence interval): 0.37 (0.14-0.98)). The aggressive resuscitation group was associated with a significantly lower need for interventions, both in univariable and multivariable analysis (adjusted odds ratio 0.21 (0.05-0.84)). Increasing fluid administration categories were associated with decreasing hospital stay in univariable analysis.
CONCLUSIONS: Early moderate to aggressive FVER was associated with lower need for invasive interventions.
Levant JA, Secrist DM, Resin H, Sturdevant RA, Guth PH.
Nasogastric suction in the treatment of alcoholic pancreatitis. A controlled study.
JAMA. 1974 Jul 1;229(1):51-2.
Abstract/Text
Naeije R, Salingret E, Clumeck N, De Troyer A, Devis G.
Is nasogastric suction necessary in acute pancreatitis?
Br Med J. 1978 Sep 2;2(6138):659-60. doi: 10.1136/bmj.2.6138.659.
Abstract/Text
Fifty-eight patients with mild to moderately severe acute pancreatitis were randomly allocated to treatment with or without nasogastric suction (27 and 31 patients respectively). Intravenous fluids and pethidine hydrochloride were also given. The two groups were comparable clinically at the start of the study. There were no differences between the two groups in the mean duration of the following features: abdominal pain or tenderness; absence of bowel movements; raised serum amylase concentration; time to resumption of oral feeding; and days in hospital. Prolonged hyperamylasaemia (serum amylase greater than 0.33 mU/l) occurred in one patient in the suction group and in three patients in the non-suction group. A mild recurrence of abdominal pain after resumption of oral feeding occurred in three patients in the suction group and in two patients in the non-suction group. Two patients in the suction group developed overt consumption coagulopathy and two others pulmonary complications. No patient in the non-suction group had complications. The findings suggest that most patients with mild to moderately severe acute pancreatitis do not benefit from nasogastric suction. The procedure should be elective rather than mandatory in treating this condition.
Field BE, Hepner GW, Shabot MM, Schwartz AA, State D, Worthen N, Wilson R.
Nasogastric suction in alcoholic pancreatitis.
Dig Dis Sci. 1979 May;24(5):339-44. doi: 10.1007/BF01297118.
Abstract/Text
In order to assess the usefulness of nasogastric suction in acute alcoholic pancreatitis, 37 patients with alcoholic pancreatitis were prospectively investigated. The study failed to demonstrate efficacy of nasogastric suction in those patients with mild disease. Application of a system of prognostic signs proved useful in discriminating between mild and severe disease. Routine use of ultrasound examinations detected three pancreatic pseudocysts before they became clinically apparent. In instituting appropriate therapy in mild pancreatitis, factors such as patient comfort should be considered in the absence of proven significant value of nasogastric suction.
Fuller RK, Loveland JP, Frankel MH.
An evaluation of the efficacy of nasogastric suction treatment in alcoholic pancreatitis.
Am J Gastroenterol. 1981 May;75(5):349-53.
Abstract/Text
We evaluated the efficacy of nasogastric suction for alcohol-related pancreatitis by performing a randomized, controlled study. Twenty-one patients with pancreatitis associated with alcohol ingestion received either nasogastric suction or nothing by mouth in addition to intravenous fluids and meperidine as needed. Twenty patients completed the treatment to which they were assigned. There were no statistically significant differences between the group that received nasogastric suction and the group that did not in duration of abdominal pain, anorexia, abdominal tenderness, ileus, presence of abdominal masses, or elevated serum amylase and lipase activities and the ratio of the renal clearance of amylase to creatinine; or the number of meperidine injections requested per subject. Patients receiving nasogastric suction complained of significantly longer duration of nausea and vomiting. We conclude that nasogastric suction is not effective in the treatment of uncomplicated alcoholic pancreatitis.
Goff JS, Feinberg LE, Brugge WR.
A randomized trial comparing cimetidine to nasogastric suction in acute pancreatitis.
Dig Dis Sci. 1982 Dec;27(12):1085-8. doi: 10.1007/BF01391445.
Abstract/Text
Clinical and experimental evidence has suggested that the use of cimetidine might be harmful to patients with acute pancreatitis. We conducted a randomized study comparing cimetidine to nasogastric (NG) suction in 95 patients with 103 episodes of mild to moderately severe, acute or relapsing pancreatitis (86.4% alcohol related). The groups were comparable on entry to the study, and daily evaluation of several clinical and laboratory criteria revealed no consistent differences between the two groups. When these same criteria were evaluated for time of return to normal, if abnormal on entry to the study, no differences were found. The cimetidine group had a significantly shorter stay in the hospital than did the NG group (6.8 +/- 2.7 vs 8.5 +/- 4.8 days). Neither the incidence of relapse or complication nor the duration and extent of hyperamylasemia were significantly different between patients treated with cimetidine or NG suction. We conclude that cimetidine is safe to use in patients with mild to moderately severe alcohol-related pancreatitis, but it offers minimal advantage over NG suction.
Loiudice TA, Lang J, Mehta H, Banta L.
Treatment of acute alcoholic pancreatitis: the roles of cimetidine and nasogastric suction.
Am J Gastroenterol. 1984 Jul;79(7):553-8.
Abstract/Text
A double-blind prospective controlled study designed to determine the effectiveness of the addition of cimetidine to standard treatment of acute alcoholic pancreatitis and to determine the importance of nasogastric suction in this disorder was undertaken. Forty-five patients were randomized to one of four treatment groups: 1) group I received intravenous cimetidine plus a blinded nasogastric tube, 2) group II received intravenous cimetidine plus nasogastric suction, 3) group III received nasogastric suction plus cimetidine placebo, and 4) group IV received a blinded nasogastric tube plus cimetidine placebo. Patients were evaluated via both biochemical and clinical parameters. It was concluded that 1) cimetidine added to more traditional therapy does not hasten improvement in patients with acute alcoholic pancreatitis, 2) cimetidine may delay recovery as measured by both clinical and biochemical measurements, 3) nasogastric suction appears indicated, under most circumstances, only in those patients with ileus and/or nausea and emesis.
Navarro S, Ros E, Aused R, García Pugés M, Piqué JM, Vilar Bonet J.
Comparison of fasting, nasogastric suction and cimetidine in the treatment of acute pancreatitis.
Digestion. 1984;30(4):224-30. doi: 10.1159/000199112.
Abstract/Text
88 unselected patients with acute pancreatitis entered a randomized clinical trial comparing the therapeutic efficacy of fasting alone, nasogastric suction and fasting plus cimetidine. The disease was mild to moderate in all but 3 cases, and cholelithiasis was the main etiological factor. The number of treatment failures and complications, and the clinical outcome were similar in the three groups. However, when compared to fasting alone, nasogastric suction was shown to delay the resumption of bowel activity a mean of 11 h (p less than 0.05), prolong the duration of pain a mean of 20 h (p less than 0.01), increase analgesic needs (pentazocine lactate) a mean of 64 mg (p less than 0.05), and lengthen hospital stay a mean of 2 days (p = NS). In conclusion, cimetidine has no beneficial effects in acute pancreatitis. It is suggested that fasting alone be initially used as the simpler, safer and more economical therapy. Nasogastric suction should be reserved for patients presenting with intestinal ileus, a situation that occurred in 1 out of every 8 cases in the present series.
Sarr MG, Sanfey H, Cameron JL.
Prospective, randomized trial of nasogastric suction in patients with acute pancreatitis.
Surgery. 1986 Sep;100(3):500-4.
Abstract/Text
The efficacy of nasogastric (NG) suction was evaluated in a prospective, randomized trial in 60 patients with acute pancreatitis of mild to moderate severity. Group I, NG (29 patients) was treated with NG suction, and group II, no NG (31 patients) was treated without NG suction. The presentation, cause of pancreatitis, and clinical parameters at the time of admission of the two groups were similar. The use of NG suction had no discernible benefit during hospitalization. There were no differences in duration of abdominal pain, the interval until bowel sounds returned, the need for narcotic administration, or the length of time intravenous fluid therapy was needed. When compared with group II, no NG, patients in group I, NG tended to resume oral intake later (5.0 +/- 0.3 versus 3.9 +/- 0.5 days) and remain hospitalized longer (13.1 +/- 2.6 versus 10.7 +/- 2.0 days). The incidence of serious complications, such as pancreatic abscess, pseudocyst, biliary obstruction, or pulmonary failure, was no different between the groups. This study demonstrates that the routine use of NG suction in patients with acute pancreatitis of mild to moderate severity is of no benefit in altering the clinical course.
Marik PE, Zaloga GP.
Meta-analysis of parenteral nutrition versus enteral nutrition in patients with acute pancreatitis.
BMJ. 2004 Jun 12;328(7453):1407. doi: 10.1136/bmj.38118.593900.55. Epub 2004 Jun 2.
Abstract/Text
OBJECTIVE: To compare the safety and clinical outcomes of enteral and parenteral nutrition in patients with acute pancreatitis.
DATA SOURCES: Medline, Embase, Cochrane controlled trials register, and citation review of relevant primary and review articles.
STUDY SELECTION: Randomised controlled studies that compared enteral nutrition with parenteral nutrition in patients with acute pancreatitis. From 117 articles screened, six were identified as randomised controlled trials and were included for data extraction.
DATA EXTRACTION: Six studies with 263 participants were analysed. Descriptive and outcome data were extracted. Main outcome measures were infections, complications other than infections, operative interventions, length of hospital stay, and mortality. The meta-analysis was performed with the random effects model.
DATA SYNTHESIS: Enteral nutrition was associated with a significantly lower incidence of infections (relative risk 0.45; 95% confidence interval 0.26 to 0.78, P = 0.004), reduced surgical interventions to control pancreatitis (0.48, 0.22 to 1.0, P = 0.05), and a reduced length of hospital stay (mean reduction 2.9 days, 1.6 days to 4.3 days, P < 0.001). There were no significant differences in mortality (relative risk 0.66, 0.32 to 1.37, P = 0.3) or non-infectious complications (0.61, 0.31 to 1.22, P = 0.16) between the two groups of patients.
CONCLUSIONS: Enteral nutrition should be the preferred route of nutritional support in patients with acute pancreatitis.
Al-Omran M, Groof A, Wilke D.
Enteral versus parenteral nutrition for acute pancreatitis.
Cochrane Database Syst Rev. 2003;(1):CD002837. doi: 10.1002/14651858.CD002837.
Abstract/Text
BACKGROUND: Acute pancreatitis creates a catabolic stress state promoting a systemic inflammatory response and nutritional deterioration. Adequate supply of nutrients plays an important role to ensure optimum recovery. Total parenteral nutrition (TPN) has been the standard practice for providing exogenous nutrients to patients with severe acute pancreatitis. However, recent data suggest that enteral nutrition (EN) is feasible. Thus, a comparison of EN and TPN in patients with acute pancreatitis needs to be made.
OBJECTIVES: To compare the effect of total parenteral nutrition (TPN) versus enteral nutrition (EN) on mortality, morbidity and length of hospital stay in patient with acute pancreatitis.
SEARCH STRATEGY: Trials were identified by computerized searches of The Cochrane Controlled Trials Register, MEDLINE, and EMBASE. Additional studies were identified and included where relevant by searching Scisearch, the bibliographies of review articles and identified trials, and personal files. The search was undertaken in August, 2000 and updated in September 2002. No language restrictions were applied.
SELECTION CRITERIA: Randomized clinical trials, in which nutrition support with TPN were compared to EN in patients with acute pancreatitis.
DATA COLLECTION AND ANALYSIS: Two reviewers independently abstracted data and assessed trial quality. Information was collected on death, length of hospital stay, systemic infection, local septic complications, and other local complications.
MAIN RESULTS: Two trials with a total of 70 participants were included. The relative risk (RR) for death with EN vs TPN was 0.56 (95% CI 0.05 to 5.62). Mean length of hospital stay was reduced with EN (WMD -2.20, 95% CI -3.62 to -0.78). RR for systemic infection with EN vs TPN was 0.61 (95% CI 0.29 to 1.28). In one trial, RR for local septic complications and other local complications with EN vs TPN was 0.56 (95% CI 0.12 to 2.68) and 0.16 (95% CI 0.01 to 2.86) respectively.
REVIEWER'S CONCLUSIONS: Although there is a trend towards reductions in the adverse outcomes of acute pancreatitis after administration of EN, clearly there are insufficient data to draw firm conclusions about the effectiveness and safety of EN versus TPN. Further trials are required with sufficient size to account for clinical heterogeneity and to measure all relevant outcomes.
急性膵炎診療ガイドライン2015改訂出版委員会 編：急性膵炎診療ガイドライン 2015年 第4版、金原出版、2015.
Grewe M, Tsiotos GG, Luque de-Leon E, Sarr MG.
Fungal infection in acute necrotizing pancreatitis.
J Am Coll Surg. 1999 Apr;188(4):408-14. doi: 10.1016/s1072-7515(98)00334-2.
Abstract/Text
BACKGROUND: Anecdotal reports suggest that patients with fungal infection of necrotizing pancreatitis (NP) have worse outcomes than those with bacterial infection. Our aim was to compare the clinical course and outcomes of patients with NP infected with fungal versus nonfungal organisms.
STUDY DESIGN: Prospectively collected data on 57 patients with infected NP (1983-1995) were reviewed.
RESULTS: Seven patients (12%) developed fungal infection, and 50 (88%) developed bacterial infection. Groups had similar mean ages (60 versus 63 years) and APACHE-II scores on admission (9 each). The cause of NP was ERCP-induced in 3 of 7 with fungal infection versus 3 of 50 with bacterial infection. Patients with fungal infection had been treated with a mean of 4 different antibiotics for a mean of 23 days, and 4 of 7 (57%) required mechanical ventilation preoperatively. In addition, postoperative ICU stays were longer (20 versus 10 days), as were total hospital stays (59 versus 41 days). Mortality was higher with fungal infection; 3 of 7 patients (43%) died versus 10 of 50 patients (20%).
CONCLUSIONS: Although NP presents with similar initial severity, patients with fungal infection of NP tend to have a more complicated course and worse outcomes compared with those with bacterial infection. Low-dose antifungal prophylaxis should be added to early management of NP.
Seta T, Noguchi Y, Shimada T, Shikata S, Fukui T.
Treatment of acute pancreatitis with protease inhibitors: a meta-analysis.
Eur J Gastroenterol Hepatol. 2004 Nov;16(12):1287-93. doi: 10.1097/00042737-200412000-00009.
Abstract/Text
OBJECTIVES: Protease inhibitors are used to treat acute pancreatitis, but their effectiveness remains unclear. We performed a meta-analysis to determine whether treatment with protease inhibitors reduces overall mortality or morbidity from acute pancreatitis.
METHODS: Articles of randomized controlled trials evaluating effects of protease inhibitors for acute pancreatitis were retrieved by systematically searching Medline, the Cochrane Library and Journal@ovid databases published from January 1966 through December 2003. References of review articles were also searched manually. The main outcome in interest was the overall mortality rate from acute pancreatitis.
RESULTS: Ten studies met the inclusion criteria. Treatment with protease inhibitors did not significantly reduce the mortality rate from acute pancreatitis (pooled risk difference, -0.03; 95% confidence interval, -0.07 to 0.01). Subgroup analyses showed that treatment with protease inhibitors significantly reduced the mortality rate in patients with moderate to severe pancreatitis (pooled risk difference, -0.07; 95% confidence interval, -0.13 to -0.01) as defined by mortality rate in the control group (control mortality rate > 0.10). The decrease in mortality rate was not significant in mild pancreatitis (pooled risk difference, 0.00; 95% confidence interval, -0.04 to 0.05).
CONCLUSIONS: Treatment with protease inhibitors does not significantly reduce the mortality in patients with acute or mild pancreatitis, but may reduce the mortality in patients with moderate to severe pancreatitis.
Piaścik M, Rydzewska G, Milewski J, Olszewski S, Furmanek M, Walecki J, Gabryelewicz A.
The results of severe acute pancreatitis treatment with continuous regional arterial infusion of protease inhibitor and antibiotic: a randomized controlled study.
Pancreas. 2010 Aug;39(6):863-7. doi: 10.1097/MPA.0b013e3181d37239.
Abstract/Text
OBJECTIVES: A randomized controlled trial was conducted to clarify whether continuous regional arterial infusion (CRAI) of protease inhibitor and antibiotic could reduce mortality rate of severe acute pancreatitis (SAP).
METHODS: Seventy-eight patients with SAP were included in the study. Thirty-nine patients were treated with CRAI, 31 patients completed the study; and another group of 39 patients was treated without CRAI therapy. Groups were well matched in clinical characteristics. The CRAI patients were treated continuously with nafamostat mesylate 240 mg/d and imipenem 1 g/d for 5 days via one of the arteries perfusing the pancreas. Later, imipenem was given intravenously (0.5 g every 8 hours) for 9 days. The non-CRAI patients received imipenem (0.5 g every 8 hours) intravenously for 14 days. Statistical analysis of the intention-to-treat (ITT) group was performed.
RESULTS: Lack of septic complications was observed in 23 patients with CRAI therapy and 20 non-CRAI patients (not significant). The additional antibiotics were applied in 8 of CRAI patients and in 18 non-CRAI (ITT, P = 0.02). Mortality rate was 5.1% in CRAI and 23.1% in non-CRAI group (ITT, P = 0.02). Urgent surgical intervention was necessary in 10.3% CRAI patients and in 33.3% non-CRAI (ITT, P = 0.01).
CONCLUSIONS: The results show that CRAI of protease inhibitor and antibiotic is effective in preventing complications and in reducing mortality rate in SAP.
Hirota M, Shimosegawa T, Kitamura K, Takeda K, Takeyama Y, Mayumi T, Ito T, Takenaka M, Iwasaki E, Sawano H, Ishida E, Miura S, Masamune A, Nakai Y, Mitoro A, Maguchi H, Kimura K, Sanuki T, Ito T, Haradome H, Kozaka K, Gabata T, Kataoka K, Hirota M, Isaji S, Nakamura R, Yamagiwa K, Kayaba C, Ikeda K.
Continuous regional arterial infusion versus intravenous administration of the protease inhibitor nafamostat mesilate for predicted severe acute pancreatitis: a multicenter, randomized, open-label, phase 2 trial.
J Gastroenterol. 2020 Mar;55(3):342-352. doi: 10.1007/s00535-019-01644-z. Epub 2019 Nov 22.
Abstract/Text
BACKGROUND: Continuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear.
METHODS: This investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review.
RESULTS: There was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7-49.1% vs. 15.8%, range 3.4-39.6%, respectively, P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7-43.7% vs. 5.3%, range 0.1-26.0%, respectively, P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction.
CONCLUSIONS: CRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy.
Morimoto T, Noguchi Y, Sakai T, Shimbo T, Fukui T.
Acute pancreatitis and the role of histamine-2 receptor antagonists: a meta-analysis of randomized controlled trials of cimetidine.
Eur J Gastroenterol Hepatol. 2002 Jun;14(6):679-86. doi: 10.1097/00042737-200206000-00014.
Abstract/Text
OBJECTIVES: Acute pancreatitis is a common disorder. Histamine type-2 receptor antagonists (H2RAs) are frequently used in patients with acute pancreatitis to reduce pancreatic juice secretion. However, most of the studies on this topic have involved only a few patients, demonstrating no beneficial effect but without harm. To clarify this matter, a meta-analysis was conducted to assess the efficacy of H2RAs.
METHODS: All randomized controlled trials written in English comparing the effects of H2RAs with those of placebo were retrieved. Clinical outcome data were extracted and the results pooled to yield odds ratios or weighted mean differences. Two investigators reviewed articles independently and reached a consensus.
RESULTS: A total of 285 patients from five studies were included. Cimetidine was the only H2RA used to treat acute pancreatitis. The pooled odds ratio of complications for H2RAs versus placebo was 1.64 (95% confidence interval [CI] 0.92 to 2.92). A weighted mean difference of duration of pain was 6.96 h (95% CI -2.50 to 16.43 h) in favour of placebo.
CONCLUSIONS: Cimetidine is not more effective than placebo in reducing acute pancreatitis-related complications and the duration of pain; rather, the use of cimetidine for acute pancreatitis could be associated with higher rates of complications and pain. Until the results of a large randomized trial show otherwise, H2RAs should not be used in the absence of specific clinical indications.
Shojania KG, Duncan BW, McDonald KM, Wachter RM, Markowitz AJ.
Making health care safer: a critical analysis of patient safety practices.
Evid Rep Technol Assess (Summ). 2001;(43):i-x, 1-668.
Abstract/Text
OBJECTIVES: Patient safety has received increased attention in recent years, but mostly with a focus on the epidemiology of errors and adverse events, rather than on practices that reduce such events. This project aimed to collect and critically review the existing evidence on practices relevant to improving patient safety.
SEARCH STRATEGY AND SELECTION CRITERIA: Patient safety practices were defined as those that reduce the risk of adverse events related to exposure to medical care across a range of diagnoses or conditions. Potential patient safety practices were identified based on preliminary surveys of the literature and expert consultation. This process resulted in the identification of 79 practices for review. The practices focused primarily on hospitalized patients, but some involved nursing home or ambulatory patients. Protocols specified the inclusion criteria for studies and the structure for evaluation of the evidence regarding each practice. Pertinent studies were identified using various bibliographic databases (e.g., MEDLINE, PsycINFO, ABI/INFORM, INSPEC), targeted searches of the Internet, and communication with relevant experts.
DATA COLLECTION AND ANALYSIS: Included literature consisted of controlled observational studies, clinical trials and systematic reviews found in the peer-reviewed medical literature, relevant non-health care literature and "gray literature." For most practices, the project team required that the primary outcome consist of a clinical endpoint (i.e., some measure of morbidity or mortality) or a surrogate outcome with a clear connection to patient morbidity or mortality. This criterion was relaxed for some practices drawn from the non-health care literature. The evidence supporting each practice was summarized using a prospectively determined format. The project team then used a predefined consensus technique to rank the practices according to the strength of evidence presented in practice summaries. A separate ranking was developed for research priorities.
MAIN RESULTS: Practices with the strongest supporting evidence are generally clinical interventions that decrease the risks associated with hospitalization, critical care, or surgery. Many patient safety practices drawn primarily from nonmedical fields (e.g., use of simulators, bar coding, computerized physician order entry, crew resource management) deserve additional research to elucidate their value in the health care environment. The following 11 practices were rated most highly in terms of strength of the evidence supporting more widespread implementation. Appropriate use of prophylaxis to prevent venous thromboembolism in patients at risk; Use of perioperative beta-blockers in appropriate patients to prevent perioperative morbidity and mortality; Use of maximum sterile barriers while placing central intravenous catheters to prevent infections; Appropriate use of antibiotic prophylaxis in surgical patients to prevent postoperative infections; Asking that patients recall and restate what they have been told during the informed consent process; Continuous aspiration of subglottic secretions (CASS) to prevent ventilator-associated pneumonia; Use of pressure relieving bedding materials to prevent pressure ulcers; Use of real-time ultrasound guidance during central line insertion to prevent complications; Patient self-management for warfarin (Coumadin) to achieve appropriate outpatient anticoagulation and prevent complications; Appropriate provision of nutrition, with a particular emphasis on early enteral nutrition in critically ill and surgical patients; and Use of antibiotic-impregnated central venous catheters to prevent catheter-related infections.
CONCLUSIONS: An evidence-based approach can help identify practices that are likely to improve patient safety. Such practices target a diverse array of safety problems. Further research is needed to fill the substantial gaps in the evidentiary base, particularly with regard to the generalizability of patient safety practices heretofore tested only in limited settings and to promising practices drawn from industries outside of health care.
Jakobs R, Adamek MU, von Bubnoff AC, Riemann JF.
Buprenorphine or procaine for pain relief in acute pancreatitis. A prospective randomized study.
Scand J Gastroenterol. 2000 Dec;35(12):1319-23. doi: 10.1080/003655200453692.
Abstract/Text
BACKGROUND: To assess the analgesic efficacy and side effects of buprenorphine and procaine in patients with acute pancreatitis.
METHODS: Forty patients (average age, 50 years; 23 male) with acute pancreatitis or an acute bout of a chronic pancreatitis were prospectively randomized to receive buprenorphine or procaine for pain relief. Both analgesics were administered as constant intravenous (i.v.) infusions and additional analgesics were given on demand. Pain scores were assessed on a visual analogue scale. Close clinical control and laboratory checks were performed during the three-day study period.
RESULTS: Patients receiving buprenorphine were significantly less likely to demand additional analgesics (1 versus 14 patients; P < 0.0001). The pain scores for patients in the buprenorphine group were significantly lower over the treatment period in comparison to procaine (P < 0.05). The reduction of pain score was significantly greater during the initial two treatment days using buprenorphine (day 1: 55 versus 25, P < 0.0001; day 2: 62 versus 40, P = 0.005). Side effects were comparable for both groups with the exception of a slightly higher sedation rate under buprenorphine.
CONCLUSIONS: Constant i.v. application of buprenorphine is more effective than the recommended procaine for pain relief in acute pancreatitis.
Kahl S, Zimmermann S, Pross M, Schulz HU, Schmidt U, Malfertheiner P.
Procaine hydrochloride fails to relieve pain in patients with acute pancreatitis.
Digestion. 2004;69(1):5-9. doi: 10.1159/000076541. Epub 2004 Jan 30.
Abstract/Text
BACKGROUND: Several analgesics are in use for pain control in patients with acute pancreatitis. Procaine hydrochloride (procaine) has a long tradition and is recommended by the German Society of Gastroenterology and Metabolic Diseases for pain treatment in patients with acute pancreatitis. There is no controlled trial showing that procaine could be effective for pain treatment.
METHODS: In an open, randomized, controlled trial, 107 patients (76 male, 31 female; mean age 45 +/- 12 years) were included and randomized either to receive procaine (n = 55) or pentazocine (n = 52) for pain relief. Procaine 2 g/ 24 h was administered by continuous intravenous infusion, pentazocine 30 mg was administered every 6 h as a bolus intravenous injection. Pentazocine was additionally administered on demand whenever required in patients of both treatment groups and its total consumption was recorded. Pain scores were assessed twice daily on a visual analogue scale.
RESULTS: Patients receiving procaine were significantly more likely to request additional analgesics compared to patients treated with pentazocine alone, 98 vs. 44%, respectively (p < 0.001). Procaine did not reduce the amount of pentazocine required for pain control. The amount of pentazocine given in both groups was not statistically significantly different. Recorded pain scores were significantly lower (p < 0.001) in patients in the pentazocine group during the first 3 days of analgesic treatment. From day 4 on there was no significant difference in pain scores among the two groups.
CONCLUSION: Thus, intravenous procaine treatment is not effective for pain control in patients with acute pancreatitis.
Copyright 2004 S. Karger AG, Basel
Peiró AM, Martínez J, Martínez E, de Madaria E, Llorens P, Horga JF, Pérez-Mateo M.
Efficacy and tolerance of metamizole versus morphine for acute pancreatitis pain.
Pancreatology. 2008;8(1):25-9. doi: 10.1159/000114852. Epub 2008 Jan 31.
Abstract/Text
BACKGROUND/AIMS: Morphine has been contraindicated for pain treatment in acute pancreatitis because of its presumed opioid-induced sphincter of Oddi dysfunction. However, scientific evidence supporting a deleterious influence on the clinical course is absent. This pilot study was undertaken to evaluate the efficacy and adverse events of metamizole versus morphine in acute pancreatitis.
METHODS: 16 patients with acute pancreatitis were randomized to receive 10 mg/4 h s.c. (n = 8) morphine or 2 g/8 h i.v. (n = 8) metamizole. Pain scores were recorded every 4 h during 48 h after admission by a Visual Analogue Scale. Pethidine was additionally administered as a rescue therapy.
RESULTS: 75% of patients achieved pain relief in the metamizole group versus 37.5% in the morphine group within 24 h of hospitalization (6/8 vs. 3/8; p: n.s.). The mean time to achieve pain relief was shorter in the metamizole group (10 +/- 6.6 vs. 17 +/- 18.3 h; p: n.s.). At the end of the study, 75% of patients achieved pain relief in the metamizole group versus 50% in the morphine group. Three patients in each group needed pethidine: 2 out of 3 achieved pain control in the metamizole group vs. 0 out of 3 in the morphine group.
CONCLUSIONS: Intravenous metamizole shows a non-significant association with a quicker pain relief than morphine s.c. in acute pancreatitis. A larger randomized controlled trial should be desirable to confirm this result. and IAP.
Copyright 2008 S. Karger AG, Basel.
