AKUT PANKREATIT. Roland Andersson 11 april 2014, Lund. Fall 1. 1. Evidensbaserade riskfaktorer för svår akut pankreatit?



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AKUT PANKREATIT Roland Andersson 11 april 2014, Lund Fall 1 47-årig kvinna med övervikt, BMI 31, insulinbehandlad diabetes mellitus, inkommer med ett knappt dygns anamnes på smärtor i övre delen av buken. Pat har en känd gallstenssjukdom med upprepade stenanfall, ultraljudsverifierade multipla små konkrement i gallblåsan och står på väntelista för op. För knappt 3 mån sedan var pat inlagd pga en lindrig akut pankreatit men någon kolecystektomi har ännu ej kommit till stånd. Vid inkomsten har pat uttalade smärtor upptill i buken, bltr 90/65, puls ca 120/min och pankreasspecifikt amylas 15 ukat/l, CRP 147, bilirubin 53 och övriga leverparametrar något förhöjda. Diskussion 1. Evidensbaserade riskfaktorer för svår akut pankreatit 1. Fetma 2. Underliggande gallstenssjukdom 3. Lågt blodtryck vid inläggning 4. CRP-nivå 1. Evidensbaserade riskfaktorer för svår akut pankreatit? 1. Fetma (BMI > 30). Fetma + APACHE II (grad B) 2. Underliggande gallstenssjukdom ingen egentlig konsensus om underliggande orsak spelar någon roll (vid primärinsjuknandet) 2. Lågt blodtryck vid ankomst (hypovolemi < 100 mmhg) associerat med ökad mortalitet i predikterad svår AP, SIRS och MODS (grad A) Eckerwall et al. Clin Nutr 2006;25:497-504 Powell et al. Br J Surg 1998;185:582-87 4. CRP-nivå överstigande 150 mg/l efter 48-72 tim (grad B) 1

Fall, forts Inlägges, erhåller 2 liter 5 % glukos (40/20) under de kommande 16 timmarna. Kontroll av blodtryck och puls var 6:e timme, ingen övrig parenteral eller enteral nutrition Inga övriga undersökningar utförda under denna första observationsperiod (på vanlig vårdavdelning) Diskussion 2. Vad är mest betydelsefullt, men inte optimalt handlagt, under denna första observationsperiod? 1. Ultraljud eller CT har inte gjorts 2. Sparsam vätskeresuscitering, infrekvent kontroll av blodtryck och puls samt bristande kontroll av urinproduktion 3. Avsaknad av upprepade blodprovskontroller inkluderande leverfunktion, amylas och CRP 4. Avsaknad av enteralt/parenteralt nutritionsstöd från första början 2. Vad är mest betydelsefullt, men inte optimalt handlagt, under denna första observationsperiod? 1. Ultraljud eller CT dagundersökning, föreligger gallstenssjukdom? CT (med intravenös kontrast) indikerad med kvarstående organsvikt, tecken på sepsis, försämring, diagnostiska differentialsvårigheter, annars helst först efter 5-7 dagar (grad B) 2. Tidig vätskeresuscitering betydelsefull, hypovolemi vid ankomst = ökad mortalitet (grad A) Eckerwall G et al. Clin Nutr 2006;25:497-504 3. CRP grad B, oklart värde de första 24 tim 4. Inga evidens om något värde av enteral/parenteral nutrition de första 1-2 dagarna Fall, forts Följande morgon har patienten bristande urinproduktion (600 ml sedan inläggningen 16 tim tidigare), blodtryck 95/60, puls 98, temp 38.1 o C, tachypnoisk, CRP 295, kreatinin 167 Diskussion 3. Vilket/-a av följande förslag ska prioriteras? 1. Cirkulatorisk resuscitering 2. Nutrition patienten är i katabolt tillstånd 3. Ultraljud eller CT omfattningen av pankreatiten och den inflammatoriska processen? 4. Antibiotika CRP ökar, febril patient 3. Vilket/-a av följande förslag ska prioriteras? 1. Cirkulatorisk resuscitering (hypovolemi) (grad A) Eckerwall G et al. Clin Nutr 2006;25:497-504 2. Nutrition tidig enteral nutrition möjlig, förbättrad metabol kontroll vid SAP, oklart om det inflammatoriska svaret kan påverkas och oklara andra systemeffekter vid tidig start (grad B) Eckerwall G et al. Ann Surg 2006;244:959-65 Omedelbart oralt intag möjligt utan biverkan, minskar vårdtid med 1/3 vid mild AP (grad A) Eckerwall G et al. Clin Nutr 2007;26:758-63 Probiotika kan inte rekommenderas för närvarande (grad A) Besselink MG et al. Lancet 2008;371:651-59 3. Ultraljud eller CT dagtid, gallstenssjukdom? CT (IV kontrast) kvarstående organsvikt, sepsis, försämring, diagnostiska svårigheter, om möjligt inte förrän minimum 5-7 dagar (grad B) 4. Antibiotika profylaktisk antibiotika rekommenderas inte vid SAP (grad A) Dellinger et al. Ann Surg 2007;245:674-83 Isenmann et al. Gastroenterology 2004;106;997-1004 2

Andra dagen efter inläggning är CRP 350, temperaturen 38.9 o C, buken uppspänd, buksmärta, buktryck 18 mmhg. Ökade transaminaser men nästan normalt bilirubin (23) Diskussion 4. Plan? 1. Patienten till IVA behov av intensivvård, risk respiratorisk svikt 2. Risk för abdominellt kompartmentsyndrom, laparotomi för dekompression 3. Antibiotika 4. CT och ERC 4. Plan? 4. Plan? 1. Behandling på specialistenhet och intensivvård, multidisciplinärt team för att monitorera och stödja organfunktion (grad B) 2. Ingen indikation laparotomi 3. Antibiotika profylaktisk antibiotika rekommenderas inte vid SAP (grad A) 4. Ultraljud och CT se tidigare (grad B) ERCP och ES rekommenderas vid svår gallstensorsakad AP med misstanke på kvarvarande koledochuskonkrement, kvarstående gallvägsobstruktion och tecken på kolangit (grad A) 1. Behandling på specialistenhet och intensivvård, multidisciplinärt team för att monitorera och stödja organfunktion (grad B) 2. Ingen indikation laparotomi 3. Antibiotika profylaktisk antibiotika rekommenderas inte vid SAP (grad A) 4. Ultraljud och CT se tidigare (grad B) ERCP och ES rekommenderas vid svår gallstensorsakad AP med misstanke på kvarvarande koledochuskonkrement, kvarstående gallvägsobstruktion och tecken på kolangit (grad A) Dag 5: inotropt stöd, respirator, abdominellt tryck 22 mmhg, temperatur 39.1 o C, oligurisk. CT (utan kontrast; kreatinin 290) extensivt peripankreatiskt ödem, viss mängd ascites Diskussion 5. Plan? 1. Operation 2. Antibiotika CRP, ökad temperatur 3. Fortsatt konservativ expekterande/ observerande behandling på IVA 4. Perkutant dränage 3

5. Plan? 1. Kirurgisk nekrosektomi bör skjutas till minst 3-4 veckor efter insjuknande (grad B) 2. Minimal-invasiv teknik, organbevarande (grad B); infekterad pankreasnekros prognostiskt negativ indikation för intervention (grad B) 3. Antibiotika om positiv odling (= behandling) 4. Organunderstödjande behandling 5. Perkutant dränage om större vätskekomponent (grad B) Långsam stabilisering, återkomst av urinproduktion, extuberad dag 8 CT visar perfusion av enbart delar av corpus och cauda, extensivt peripankreatiskt ödem Maximal organunderstödjande behandling CT dag 16 minimala tecken på genomblödning i corpus-cauda, tecken på pankreas/peripankreatisk infektion med gasbubblor, mindre mängd ascitesvätska, temp 39.5 o C, ånyo försämrad Diskussion 6. Plan? 1. Perkutant dränage 2. Laparotomi eller minimalinvasiv nekrosektomi 3. Fortsatt konservativ behandling antibiotika, vätska, nutrition 6. Plan? 1. Perkutant dränage som steg 1 om större vätskekomponent (grad B) 2. Se tidigare - kirurgisk nekrosektomi helst efter vecka 3-4, organbevarande (grad B), infekterad pankreasnekros prognostiskt negativt och indikation för intervention (grad B) 3. Otillräckligt Under det fortsatta postoperativa förloppet förbättras patienten gradvis och kan hemskrivas efter ytterligare 3 veckor Återinlagd 4 veckor senare pga utspänd buk, ingen feber 4

Diskussion 7. Vad göra? 1. Expektans 2. Transgastriskt endoskopiskt eller perkutant dränage (pigtail) 3. Transpapillärt dränage 4. Öppen kirurgi 7. Vad göra? Behandling av pseudocystor icke infekterade 1. Asymptomatisk pseudocysta konservativ behandling (grad B) 2. Symptomatisk minimalinvasiv, gradvis step-up (perkutan, endoskopisk, kirurgisk; grad B) 3. Transpapillärt dränage (ERCP) om pseudocystan kommunicerar med pankreasgången (grad C) 4. EUS-riktat transintestinalt dränage (grad C) Kolecystektomi vid akut gallstenspankreatit 1. Kolecystektomi (om möjligt laparoskopiskt) med intraoperativ kolangiografi vid samma vårdtillfälle eller omedelbart därefter (inom 2-4 veckor; grad A) 2. Ingen ERCP eller MRCP nödvändig preoperativt vanligen har koledochuskonkrementet avgått eller kan hanteras intra- eller postoperativt (ERCP; grad B) Definition acute pancreatitis Acute inflammatory process in the pancreas with varying degrees of local involvement or remote organ systems Severe acute pancreatitis (15-20 %) defined as the occurrence of organ failure > 3 Ranson criteria, > 8 APACHE II-points or local complications (pancreatic necrosis, pseudocyst, pancreatic abscess) Atlanta Classification. Arch Surg 1993;128:586-590 Severe acute pancreatitis should not include patients with organ failure resolving within 48 hrs. Gut 2005;54:suppl 3:1-9 Identifying early and late phases; mild, moderate or severe disease revised Atlanta Classification Gut 2013; 62:102-111 Definition revised Atlanta Classification Grades of severity Mild acute pancreatitis No organ failure No local or systemic complications Moderately severe acute pancreatitis Organ failure that resolves within 48 h (transient organ failure) and/or Local or systemic complications without persistent organ failure Severe acute pancreatitis Persistent organ failure (> 48 h), single/multiple organ failure Gut 2013; 62:102-11 5

Definition revised Atlanta Classification Phases of disease Early phase Resolves within 1-2 weeks; persistent SIRS = increased risk of developing organ failure Late phase Persistent or systemic inflammation, local complications, occurs only in moderately severe or severe acute pancreatitis Gut 2013; 62:102-11 Key recommendations Stratification of severity CECT scanning Prophylactic antibiotics Endoscopic sphincterotomy (biliary AP) Timing of cholecystectomy (biliary) Surgery (sterile necrosis) FNA (infected pancreatic necrosis) Enteral nutrition Efficacy of antiproteases Speciality centers for severe AP Compliance Variable Variable Mostly Variable Variable, increasing Mostly Not applicable Mostly Not applicable Variable Awareness high (German surgeons), compliance intermediate Lankisch PG. Pancreatology 2005;5:591-593 Foitzik T. Pancreatology 2007;7:80-85 Adherence to best practice guidelines in the treatment of severe pancreatitis poor Vlada AC. HPB 2013; 15:822-27 Implementation more difficult the more interventional and dependent on factors not controlled by the physician. Simplified audit goals after implementation. Andersson R. Scand J Gastroenterol 2008;43:515-517 Non-compliance with guidelines frequent Examples from recommendations on timing of cholecystectomy in acute gallstone pancreatitis Compliance (cholecystectomy ES recommended during initial admission or within three weeks) in a Dutch study (308 patients with mild biliary pancreatitis) only performed in 53 %. The delay carry a substantial risk of recurrent biliary events Bakker OJ et al. BJS 2011; 98:1446-54 Sun E et al. JOP 2013; 14: 221-27 Lack of early severity classification, differences in standard care in a Swedish national survey Andersson B et al. Scand J Gastroenterol 2012; 47:1064-70 Controversies and questions in the management Guidelines for the management - Coming recommendations from SIS-E and the Scandinavian Surgical and Gastroenterological Societies Prognostic factors of value? Severity prediction? Diagnostics type and timing? Systemic inflammatory response vs. organ failure? Fluid resuscitation when, what and how? Nutrition when, what and how? Antibiotics preventive use indicated? 6

Controversies and questions in the management The role of the gut? Any pharmacologic or medical intervention of use? ERC sphincterotomy: indication and timing? Cholecystectomy timing? Necrosectomy indication and timing? Management of late complications? Management in a highly specialised unit? Levels of evidence Ia. Ib. IIa. IIb. III. IV. Evidence obtained from meta-analysis of randomized controlled trials. Evidence obtained from at least one randomized controlled trial Evidence obtained from at least one well-designed controlled study without randomization Evidence obtained from at least one type of well-designed quasiexperimental study. Evidence obtained from well-designed non-experimental descriptive studies such as comparative studies, correlation studies and case studies. Evidence obtained from expert committee report or opinions or clinical experiences of respected authorities. Eccles M et al. BMJ 1996;312:760-762 Grading of recommendations Grade A = Strong evidence that requires a meta-analysis of randomized controlled trials or at least one randomized controlled trial (evidence categories Ia, Ib). Grade B = Intermediate evidence, requires non-randomized clinical studies (evidence categories IIa, IIb, III). Grade C = Low evidence, requires evidence from expert committee reports or opinions or clinical experiences of respected authorities, in the absence of directly applicable clinical studies of good quality (evidence categories IV). Incidence and etiology Incidence about 300/10 6 inhabitants and year in Scandinavia 80-85 % mild AP, 15-20 % severe AP (assoc. mortality 10-15 %) Appelros S et al. Br J Surg 1999;86:465-470 Andersson R et al. Scand J Gastroenterol 2004;39:891-894 Etiology dominated by gallstones (35-50 %) and alcohol (20-30 %) followed by metabolic disorders and post-ercp pancreatitis (grade B) Autoimmune pancreatitis and hereditary pancreatitis should be recognized due to specific demands on both treatment and surveillance (grade B) The percentage of idiopathic acute pancreatitis should not exceed 15-20 % following thorough work-up (grade C) Cost for health care and loss of production Cost for treating acute pancreatitis are high, especially in severe cases with long ICU stay. Overall hospital cost and cost for loss of production corresponding to 4.1 million EUR/million inhabitants (Sweden) Andersson B et al. Scand J Gastroenterol 2013; Early online 1-7 Diagnosis recommendation 1. Diagnosis (typical symptoms, amylase level > 3 times upper level of normal; lipase > 2 upper level of normal) should be established within 48 hours (grade C) 2. Contrast enhanced CT (CECT) scanning limited to predicted severe acute pancreatitis and to be performed after one week of disease unless certainty of diagnosis exists. Ultrasound limited to diagnosis of cholelithiasis (grade B) 7

Prognostic factors Clinical assessment (including Grey Turner, Cullen signs, pleural effusion on chest X-ray etc) (grade C) Obesity - BMI > 30. Obesity factor + APACHE II (grade B) Age - Age exceeding 65 years of age (grade B) Scoring symptoms - Ranson, Glasgow scores - Atlanta classification - APACHE II - SOFA (sepsis-related organ failure assessment), Marshall score (overall grade max B) Biochemical test - CRP exceeding 150 mg/l at 48-72 hrs - Pro-calcitonin (PCT) > 3.8 ng/ml predicting severe disease (grade B) Imaging - Contrast-enhanced computed tomography (CECT) indicated when persisting organ failure, signs of sepsis, deterioration, day 4-10. Balthazar score (grade B) Recommendation prognostic factors (grade B) At admission and before 24 hrs after onset of pain: Clinical assessment of severity (tachypnea, tachychardia, fever, peritonitis, hypertension, Grey Turner) BMI > 30 APACHE II > 8 Pleural effusion (chest x-ray) Signs of organ dysfunction Recommendation prognostic factors (grade B) 48 hours after onset of pain: Clinical severity assessment Ranson/Glasgow > 3 CRP > 150 mg/l Multiple or persistent organ dysfunction mild acute pancreatitis Nutritional support in acute pancreatitis No specific medication influencing the course of disease (grade A) Adequate fluid resuscitation and prevention of hypoxemia in order to prevent an increase in severity (grade C) Adequate pain relief (grade C) Oral/enteral feeding shortens hospital stay (grade A) Immediate oral feeding in acute pancreatitis? I Immediate oral feeding vs. pancreatic rest Inclusion < 48 hrs, APACHE II < 8, CRP < 150 mg/l (= Atlanta mild) Hospital stay, inflammatory response, tolerance (abdominal pain, gastrointestinal symptoms) Eckerwall G et al. Clin Nutr 2007;26:758-763 8

Nutritional support in acute pancreatitis Immediate oral feeding in acute pancreatitis? II Hospital stay No difference in inflammatory response, abdominal pain, gastrointestinal symptoms or complications Reduction of hospital stay by 2 days (1/3) corresponding to a yearly saving of 2.1 million Euro (Sweden; 9.1 million inhabitants) Clin Nutr 2007;26:758-763 Inflammatory response in predicted severe acute pancreatitis Severe acute pancreatitis - management Inflammatory Normal Anti-inflammatory Hyperinflammatory state SIRS Early MODS Hypoinflammatory state (CARS) Infection late MODS Time course Course in acute pancreatitis First hit Acute pancreatitis - tissue injury MODS SIRS Second hit Recovery MODS, infection Mortality Recovery Pathogenesis Acute inflammatory response The magnitude of the acute inflammatory response and release of cytokines and mediators correlate with the development of systemic complications and organ dysfunction De Beaux AC et al. Br J Surg 1996;83:349-353 McKay CJ et al. Br J Surg 1996;83:919-923 Ogawa M. Pancreas 1998;16:312-315 Lundberg AH et al. Ann Surg 2000;231:213-222 Persistent SIRS associated with MODS and mortality, an early indicator of severity in acute pancreatitis Mofidi R et al. Br J Surg 2006;93:738-744 Mortality 9

Prediction of severity in acute pancreatitis using artificial neural networks (ANN) I Prediction of severity in acute pancreatitis using artificial neural networks (ANN) II ANNs - 6 of 23 potential risk variables relevant for severity prediction: duration of pain until admission, kreatinin, hemoglobin, alanin, aminotransferase, heart rate, white blood cell count ANNs superior to both APACHE II and a linear regression model in predicting severity of AP Andersson B et al. Pancreatology 2011; 11:328-35 Andersson B et al. Pancreatology 2011; 11:328-35 Medical treatment of severe acute pancreatitis Hypovolemia (< 100 mmhg) at admission correlates with increased mortality in predicted severe AP Hypovolemia SIRS, and increased endothelial barrier permeability, correlating with the magnitude of the proinflammatory response Andersson B et al. Pancreatology 2006; 6:536-41 Eckerwall et al. Clin Nutr 2006;25:497-504 Powell et al. Br J Surg 1998;185:582-587 Menger et al. J Hepatobil Pancreat Surg 2001;8:187-194 Minimizing ischemia/reperfusion injury by early and carefully monitored fluid resuscitation (cristalloids and/or colloids), the course of disease can be influenced (grade B) Bild Acute pancreatitis enteral nutrition Early enteral nutrition in acute pancreatitis is feasible, reduce costs, decrease septic complications and infected pancreatic necrosis, decrease hospital stay, inflammatory response and improves gut function Kalfarentzos F et al. Br J Surg 1997;84:665-669*) Windsor AC et al. Gut 1998;42:431-435*) Nakad A et al. Pancreas 1998;17:187-193*) Olah A et al. Nutrition 2002;18:259-262 Gupta R et al. Pancreatology 2003;3:406-413 Zhao G et al. World J Gastroenterol 2003;9:2105-2109 Modena JT et al. Pancreatology 2006;6:58-64 *) limited number of patients, delay until initiation of treatment, varying severity, nutritional formula generally not defined Acute pancreatitis enteral nutrition Consensus on enteral nutrition (EN) preferred over parenteral nutrition (PN) when feasible Enteral vs. Parenteral Nutrition for Acute Pancreatitis. The Cochrane Collaboration 2010. Al-Omran M et al. International Consensus Guidelines for Nutrition Therapy in Pancreatitis. Mirtallo JM et al. JPEN 2012; 36:284-91 ESPEN Guidelines for Enteral Nutrition. Clin Nutr 2006; 25:275-84 10

Nutritional support in acute pancreatitis Position of the nutritional tube? Nasogastric enteral nutrition reported successful in SAP (22/26) Eatock FC et al. Int J Pancreatol 2000;28:23-29 EN well tolerad by nasojejunal and nasogastric routes in SAP, no aggravation of the pancreatitis Kumar A et al. J Clin Gastroenterol 2006;40:431-434 Nasogastric early enteral nutrition (standard formula) feasible and improves metabolic (blood glucose) control in patients with predicted SAP (< 48 hrs, APACHE II > 8, CRP > 150 mg/l, CT) Eckerwall G et al. Ann Surg 2006;244:959-965 Enteral nutrition First choice if possible (gradual step-up), balanced by TPN (grade A) A nasogastric nutritional tube can be used (grade B) At present not enough data to recommend immunonutrition in severe AP (grade C) Lessons learned from critical illness in general (glutamine, low dose steroids, intensive insulin treatment) (grade B) No specific medical treatment to be recommended (protease inhibitors, somatostatin analogs, continuous hemodiafiltration etc) (grade A) Medical treatment Probiotics Initial experimental and clinical studies (Olah A et al. Br J Surg 2002;89:1103-1107) promising Increased mortality and bowel ischemia following multi species (n = 6) probiotics together with nasojejunal enteral feeding in the PROPATRIA study Besselink MG et al. Lancet 2008;371:651-659 Recommendation: At present probiotics cannot be recommended in the management (grade A) Prophylactic antibiotic treatment I A gradual change towards a more selective use Prophylactic antibiotics to be used in predicted severe acute pancreatitis Golub et al. J Gastrointest Surg 1998;2:496-503 Bassi et al. J Hepatobil Pancreat Surg 2001;8:211-215 Increased risk of fungal infections associated with increase in mortality Isenmann. World J Surg 2002;26:372-376 Only carbapenems (penetrating pancreatic tissue) of proven value Heinrich S et al. Ann Surg 2006;243:154-168 Prophylactic antibiotics do not prevent infection, pancreatic necrosis or associated mortality Masaki et al. Br J Surg 2006;93:674-684 Medical treatment Prophylactic antibiotic treatment II No significant advantages by the administration of prophylactic antibiotics Delinger et al. Ann Surg 2007;245:674-683 Isenmann et al. Gastroenterology 2004;126:997-1004 Recommendation Prophylactic antibiotic use not to be recommended in severe acute (necrotizing) pancreatitis (grade A) Prophylactic antibiotic use should not (routinely) be recommended in the management of predictive severe (necrotizing) pancreatitis UK Guidelines. Gut 2005;54(suppl 3):ii1-ii9 Level Ia evidence are available but inconsistent 11

Bild ERCP indications and timing - recommendation (grade A) Early (usually within 72 hrs) ERCP and ES recommended in severe gallstone-induced acute pancreatitis with suspected bile duct stones and persistent biliary obstruction or signs of cholangitis Van Geenen EJ et al. Pancreas 2013; 42:774-80 Percutaneous drainage of peripancreatic fluid collections - recommendations Acute fluid collections no drainage indicated (grade B) Suspicion of infected pancreatic necrosis, abscess or infected pseudocyst percutaneous catheter drainage in order to: 1. drain all free fluid/pus 2. obtain bacteriological culture (grade B) Minimally invasive management of necrotizing pancreatitis Percutaneous catheter drainage as primary treatment for necrotizing pancreatitis 56 % required no additional surgical necrosectomy after PCD in 384 patients with necrotizing pancreatitis (71 % infected, mortality 15.4 %) van Baal MC et al. Systematic review. BJS 2011;98:18-27 Peritoneal lavage for severe acute pancreatitis does not confer a clinical benefit (systematic review) Dong Z et al. World J Surg 2010;34:2103-8 62 % of patients with necrotizing pancreatitis can be treated without intervention, mortality 15 %. In infected necrosis, delayed intervention and catheter drainage as first treatment improves outcome van Santvoort HC et al. Gastroenterology 2011; 141:1254-63 A step-up approach or open necrosectomy for necrotizing pancreatitis? A minimally invasive step-up approach, compared with open necrosectomy, reduced major complications and mortality in patients with necrotizing pancreatitis and infected necrotic tissue (RCT) N Engl J Med 2010; 362:1491-1502 12

Pancreatic necrosectomy diagnosis, timing and extent Infected pancreatic necrosis represent a prognostic factor and an indication for intervention (grade B) Diagnosis of infected necrosis by CT or FNAB (grade B) Surgical necrosectomy postponed to at least 3rd or 4th week after onset of disease, a step-up approach often feasible and beneficial (grade B) Necrosectomy should favour an organ-preserving approach maximizing evacuation of the debris and exsudate independent of technique used (grade B) Cholecystectomy in acute gallstone pancreatitis - recommendations Cholecystectomy (if possible laparoscopically) with intraoperative cholangiography to be performed in patients with acute biliary pancreatitis at the same hospital stay or immediately thereafter. Interval cholecystectomy > 3-4 weeks increase the risk of recurrent biliary events (grade A) van Baal MC et al. Ann Surg 2012; 255:860-66 No ERCP or MRCP is needed preoperatively as potential common bile duct stones are dealt with by intra- or postoperative ERCP (grade B) Compliance (cholecystectomy or ES recommended during initial admission or within 3 weeks) in a Dutch study (308 patients with mild biliary pancreatitis) only 53 %; a delay carries a substantial risk of recurrent biliary events Bakker OJ et al. BJS 2011;98:1446-54 Management in a specialist unit and intensive care - recommendation (grade B) Management in a specialist unit with multidisciplinary team (surgery, endoscopy, intensive care, anesthesia, interventional radiology) and with ICU for monitoring and organ supportive care Management of pseudocysts following acute pancreatitis (non-infected) - recommendations Asympatomatic-conservative management (grade B) Symptomatic- minimally invasive, gradual step-up percutaneous, endoscopic, surgical (grade B) Transpapillary drainage (ERCP); pseudocyst communicating with pancreatic duct (grade C) EUS-guided transintestinal drainage (grade C) Major hemorrhagic complications in acute pancreatitis Major hemorrhagic complications are rare but clinically important, occurring in 1.0 %, overall mortality rate 1/3, preferentially when occurring after more than 7 days Overall increasing mortality in severe acute pancreatitis three times. Sentinel bleeding frequent in cases with major postoperative bleeding (angiography!) (grade B) Andersson E et al. Br J Surg 2010;97:1379-84 Exocrine and endocrine dysfunction short- and long-term results - recommendation (grade B) Endocrine and exocrine insufficiency frequent (20-30 %) following severe acute pancreatitis, correlating to the extent of necrosis. Slight recovery by time (excluding alcohol-induced and recurrent pancreatitis) 13

Quality of life after acute pancreatitis - recommendation (grade B) Recovery following severe acute pancreatitis usually prolonged. Long-term quality of life (usually measured by SF-36) though good, often comparable with a healthy control group Andersson B et al. World J Gastroenterol 2010; 16:4944-51 Audit goals Assessment of etiology in all patients with a maximum of 15-20 % idiopathic acute pancreatitis (grade B) Correct diagnosis and severity stratification within 48 hrs (grade B) Patients with predicted severe acute pancreatitis should receive adequate and well monitored initial fluid resuscitation, if needed in a high-dependency or intensive care unit (grade B) Radiological facilities available for diagnosis and management of complications (grade A) Facilities for early ERCP when indicated (grade A) Early cholecystectomy in all fit patients with acute biliary pancreatitis (grade A) Mortality less than 15 % in severe acute pancreatitis (grade B) Management of patients with severe acute pancreatitis and complications in a specialist unit with multidisciplinary competence and ICU facilities (grade B) 14