Acute Pancreatitis Falk Symposium 161 Dresden 12.10.2007
Incidence of Acute Pancreatitis (Malmö) Lindkvist B, et al Clin Gastroenterol Hepatol 2004;2:831-837 Gallstones Alcohol
AGA Medical Position Statement on Acute Pancreatitis AGA Technical Review on Acute Pancreatitis Gastroenterology 132:2019-2044;2007 Limited well-designed controlled clinical trials Guidelines must include less solid evidence-based recommendations, including a wealth of expert opinion Acute pancreatitis is a disease of such variability that it cannot be effectively managed by following blindly any recommendations
Diagnosis of Acute Pancreatitis CRP blood glucose History and clinical symptoms Diagnostic Procedures serum lipase + transaminases abdominal ultrasound Staging of Severity serum calcium pulse and blood pressure arterial blood gas renal function ERCP detection of complications CT-scan in case of deterioration
Obesity as risk factor for severe pancreatitis 70 60 % 50 40 30 20 10 Local Complications Organ Failure Deaths 0 normal 26-30 >30 BMI Johnson et al. Pancreatology 4:1-6;2004, De Waele et al Pancreas 32:343-45;2006
Effect of SIRS on survival in severe pancreatitis SIRS no SIRS n Survivors (%) n Survivors (%) p Admission 87 74 (85) 34 34 (100) 0.019 24 h 45 35 (78) 76 73 (96) 0.002 48 h 32 21 (66) 89 87 (98) <0.001 Persistent 27 17 (63) 94 91 (97) <0.001 SIRS: Pulse rate >90/min; Respiratory rate >20/min oder PaCO 2 >32 mmhg; Temperature >38C ; WBC >12000/mm 3 Buter et al. Brit J Surg 89, 2002
Indicators of severity of acute pancreatitis Duration of SIRS (heart rate, respiratory status, temperature, WBC) and organ failure during first week after diagnosis determines course and prognosis Resolving of SISR and organ failure after 48h suggests good prognosis CD Johnson et al Gut 53:1340;2004, A Buter et al Br J Surg 89:298;2002 Mofidi R et al Br J Surg 93:738;2006, AGA, Gastroenterology 132;2007
Indicators of severity of acute pancreatitis Scoring systems (Ranson, Glasgow, Apache) present high false-positive rates The judgment of an experienced clinician can also be used to estimate prognosis The wisest choice is to incorporate all available information into estimate of prognosis CD Johnson et al Gut 53:1340;2004, A Buter et al Br J Surg 89:298;2002 Mofidi R et al Br J Surg 93:738;2006, AGA, Gastroenterology 132;2007
Acute Pancreatitis
CT scan and necrosis of the pancreas: problem of definition when the radiologist says pancreatic necrosis is present, this could just be nonenhancement of pancreatic tissue and does not necessarily represent irreversible pancreatic necrosis. E.J. Balthazar, Radiology;223:603; 2002 W. Traverso and R. Kozarek, J Gastrointest Surg 9:436-439; 2005
Confusion in the Imaging Ranks Poor interobserver agreement on CT findings in acute pancreatitis Besselink, Pancreas 33:331;2006: in only 4% did 5 radiologists agree on the characterization of the same finding Edward L Bradley, Pancreas 33:321; 2006 : - limit imaging reports to descriptive terms - let the clinician be responsible for integrating imaging findings in to a specific clinical diagnosis No need for CT-scan in every patient, only if therapeutic consequences will follow
Acute Pancreatitis Clinical Course Phase 1 Phase 2 Necrosis of pancreatic /perpancreatic tissue SIRS Infection of necrosis (sepsis, abscess) or recovery CRP Leucocytes 0 Lipase 14 Tage
Treatment of acute pancreatitis intensive monitoring volume resuscitation treatment of pain (Pethidin, Metamizol) yes success no severe panc. mild panc. early oral refeeding treatment of organ failure prophylactic antibiotics? early enteral feeding? sepsis/ infected necrosis endoscopic therapy / surgery?
Enteral versus parenteral nutrition in acute pancreatitis Studies (Pat) Reduction of risk (95%CI) enteral versus parenteral P = Mortality 4 (151) -1% (-12 bis + 10%) 0.41 Rate of complications 3 (119) -16% (-35 bis +10%) 0.06 Rate of infection 4 (187) -15% (-26 bis -4%) 0.53 Pseudocysts, Abscess 3 (170) -12% (-24 bis 0%) 0.05 Hyperglycemia 3 (123) -21% (-36 bis -6%) 0.21 Koretz RL et al Am J Gastroenterol 102:412-429; 2007
ESPEN guidelines on nutrition in acute pancreatitis Enteral nutrition should be performed when possible (A) Even in severe, complicated pancreatitis enteral nutrition is possible ( C ) Enteral nutrition should be provided continuously for 24 h ( C ) The jejunal route is recommended if gastric feeding is not tolerated ( C ) Meier et al. Clin Nutr 25:275-284; 2006
Disturbance of gut barrier in acute pancreatitis: benefits of enteral nutrition reduced oxygenation bacterial overgrowth reduced motility MALT dysfunktion exogenous factors Pain treatment: (morphins) reduction of motility Acid blockade: ph- increase mucosal atrophy by parenteral nutrition
Hypothetical mechanism of action of enteral nutrition in acute pancreatitis Enteral nutrition Improving the tolerance of oral refeeding Prevention of refeeding pain Decreasing the risk of pain relapse Shortening the length of hospital stay Stimulation of Intestinal motility Prevention of progression in severity Petrov MS et al AM J Gastroenterol 2007;102:1-6
Enteral Nutrition in Acute Pancreatitis: Open Questions Immunmodulated nutrients (Glutamine, Arginine, n-3 fatty acids, prebiotics)? Positive effect of enteral nutrition only until 48h after onset of symptoms? Composition of diet (caloric load, protein, fat)? Nasogastric feeding better than jejunal feeding (simplicity,ease of use, low cost, early initiation of feeding)? Early enteral feeding reduces pain relapse by improving tolerance to oral feeding?
Metaanalysis of studies on prophylactic antibiotics (6/328 studies) Reference Pederzoli 1993 Sainio 1995 Schwarz 1997 Nordback 2001 Isenmann 2004 Spicak 2004 Dosage of antibiotics Imipenem 0.5 g every 8 h Cefuroxime 1.5 g, every 8 h Ofloxacin 0.2 g, twice daily with metronidazole 0.5 g twice daily Imipenem 1.0 g every 8 h Ciprofloxacin 0.4 g, twice daily with metronidazole 0.5 g twice daily Ciprofloxacin 0.2 g, twice daily with metronidazole 0.5 g, every 8 h or meropenem 0.5 g, every 8 h Duration of antibiotic use (days) 14 >14 10 >5 21 10 Mazaki T, Ishil Y, Takayama, T Br J Surg; 93:674-684,2006
Metaanalysis of studies on prophylactic antibiotics (6/328 studies) Criteria relative risk CI (95%) P = Infected necrosis 0.77 0.54, 1.12 0.173 Mortality 0.78 0.44, 1,39 0.404 Non-pancreatic infections 0.71 0.32, 1.58 0.402 Surgical intervention 0.78 0.55, 1.11 0.167 Hospital stay -5.64-11.01, -0.27 0.040 Mazaki et al, Brit J Surg 93:674-684; 2006
Early antibiotic prophylaxis (meropenem) in acute pancreatitis Early treatment (day 1.07) n=30 Late treatment (day 4.56) n=29 P Infected necrosis 4 9 0.1 Sepsis 5 13 0.03 Multiorgan failure 2 2 1 Surgery 4 11 0.05 Hospital stay (d) 18.4 ±11.3 30.4 ±17.7 0.001 Manes G et al Am J Gastroenterol 101:1348-1353; 2006
Early ERC in biliary pancreatitis Mortality OR 95% CI Severity of pancreatitis mild severe 4.64 0.62 0.22-98.1 0.27-1.41 Complications OR 0.89 0.27 95% CI 0.53-1.49 0.14-0.53 Selected studies: Neoptolemos et al., Lancet II, 1988 Fan et al., NEJM 328, 1993 Fölsch et al., NEJM 336, 1997 Ayub et al. Cochrane Database 2005
Biliary pancreatitis: Endosonography versus ERCP EUS (n=70) ERCP (n=70) Successful (n=70) Successful (n=60) Unsuccessful (n=10) CBD Stones (n=25) Successful ERCP+duct clearance No Stones (n=45) CBD Stones (n=20) Successful duct clearance No Stones (n= 50) EUS: 45 ERCPs avoided ERCP: 50 studies without demonstration of stones Liu CL et al Clin Gastroenterol Hepatol 2005;3:1238-1244
Early endoscopic intervention versus conservative management in biliary pancreatitis early endoscopic intervention early conservative management Odds Ratio (95% confidence interval) Organ failures Respiratory 7 9 0.74 (0.25 2.17) Renal 2 0 Coagulation 2 1 2.04 (0.17 23.2) Local complications Infected necrosis 2 2 1 (0.13 7.38) Acute pseudocyst 1 1 1 (0.06-16) Gallblader perforation/empyema 3 2 1.53 (0.24 9.) A. Oria et al Ann Surg 2007;245:10-17
Biliary pancreatitis: when ERC? Categorisation of patients according to clinical, chemical and morphological criteria: 1. Patients with cholangitis early ERC 2. Patients without biliary obstruction no early ERC 3. Patients with biliary obstruction without cholangitis no early ERC
Indication and optimal timing for surgery in acute pancreatitis No indication for debridement or drainage in patients with sterile necrosis Debridement or drainage in patients with infected necrosis and/or abscess confirmed by radiological evidence of gas or results of FNA - standard procedure: open operative debridement - minimal invasive techniques might be effective (lack of controlled studies) Operative necrosectomy should be delayed at least 3 weeks to allow for demarcation of necroses Besselink et al Curr Opin Crit Care 13:200-206; 2007
Aggressive endoscopic therapy for pancreatic necroses Uncontrolled, retrospective study ERP, EUS-Cystogastrostomy, daily necrosectomy, sealing of fistula (Acrylat) Endoscopic drainage of abscesses and necroses in 13 patients In 9/13 patients no operation needed no severe complications ( necrosectomy should be done carefully, with extreme caution ) S.Seewald et al. Gastrointest Endosc 62:92;2005
Acute pancreatitis: reduction in mortality 80 70 % 60 50 40 30 20 1980-85 1986-90 1991-97 10 0 Frequency of surgery Early surgery (within 72 h) Mortality Hartwig et al. J Gastrointest Surg 6, 2002
Nonsurgical treatment of severe pancreatitis M.Runzi et al. Pancreas 30:195;2005
Management of acute pancreatitis: Perspectives Large randomized trials are urgently needed on following topics: Diagnostic CT scan: often performed without need in every patient misinterpretation of fluid collections and necroses as pseudocysts Nutrition: enteral feeding could reduce incidence of complications (infected necrosis, multiorgan failure) Infection prophylaxis: still no convincing evidence on reduction of infectious complications and mortality Biliary pancreatitis: when to perform ERC? Besselink et al Curr Opin Crit Care 13:200-206; 2007 AGA, Gastroenterology 132;2007