Severe necrotizing pancreatitis. ICU Fellowship Training Radboudumc

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1 Severe necrotizing pancreatitis ICU Fellowship Training Radboudumc

2 Acute pancreatitis Patients with acute pancreatitis van Dijk SM. Gut 2017;66:

3 Diagnosis Revised Atlanta classification Abdominal pain consistent with pancreatitis Serum amylase and/or lipase at least 3 times upper limit Findings consistent with acute pancreatitis on CECT, MRI or ultrasound At least two out of three criteria Banks PA. Gut 2013;62:

4 Severity classification Mild - no local or systemic complications Moderate - local (e.g. peripancreatic fluid collections or systemic complications or transient organ failure < 48 hrs Severe - persistent organ failure > 48 hrs Banks PA. Gut 2013;62:

5 Aetiology Gallstones/sludge Alcohol Unknown Rest Medication ERCP Hypercalcaemia Hypertriglyceridemia Surgery Trauma Perform EUS later on 15% 15% 20% 50% Sludge

6 Severity prediction APACHE II score Ranson score Modified Glasgow/Imrie score SIRS criteria > 48 hrs Bedside Index for the Severity in Acute Pancreatitis Harmless in Acute Pancreatitis Score CRP Mainly used to exclude the possibility of severe pancreatitis Vasudevan S. Pancreas 2018;47:65-71

7 Treatment acute phase Fluid resuscitation Pain management (no evidence for specific pain protocol) Antibiotics and probiotics Nutrition Endoscopic retrograde cholangiography in biliary pancreatictis

8 Fluid resuscitation IAP/APA guidelines suggest using cristalloids in the form of Ringer s lactate or other balanced fluids (not confirmed in general ICU setting) End-points for early goal-directed therapy unknown - use SvO2, lactate, diuresis, capillary refill etc % (SIRS) or mg/dl (CRP) p = SIRS after 24 hrs RL NaCl 0.9% ,5 p = 0.02 N = 40 CRP after 24 hrs Wu BU. Clin Gastroenterol Hepatol 2011;9:

9 Antibiotics and probiotics prophylaxis Aim is to prevent secondary infection of pancreatic or peripancreatic necrosis - result of bacterial translocation Antibiotic prophylaxis (several RCT s) does not prevent secondary infection Probiotics increased mortality in a multicentre RCT

10 Infected pancreatic necrosis Mortality Randomized controlled trials Lim CLL. J Gastrointest Surg 2015;19:

11 Surgical intervention Extra-pancreatic infection

12 Probiotics in predicted severe acute pancreatitis Multicentre randomized DB placebo-controlled trial (N = 298) Predicted severe acute pancreatitis (AP II 8, Imrie 3, CRP > 150 mg/l) < 72 hrs of onset of symptoms probiotics vs placebo 2 td for 28 days Primary outcome composite of infectious complications during admission and 90-D follow-up Besselink MGH. Lancet 2008;371:

13 Probiotics in predicted severe acute pancreatitis Placebo Probiotics P = 0.80 P = 0.01 P = , , Infectious complications Mortality Bowel ischemia Besselink MGH. Lancet 2008;371:

14 Nutrition Enteral nutrition reduces rates of infection, organ failure and mortality compared to parenteral nutrition In patients with predicted severe pancreatitis, enteral can be limited to those who have an insufficient oral intake after 3-5 days Nasogastric feeding is non-inferior to nasojejunal feeding (3 RCT s)

15 Enteral versus parenteral nutrition in acute pancreatitis Mortality Operative intervention Al-Omran M. Cochrane Database Syst Rev 2010;1:CD002837

16 Early enteral feeding in predicted severe acute pancreatitis PYTHON trial Multicentre randomized trial (N = 208) Predicted severe acute pancreatitis (AP II 8, Imrie 3, CRP > 150 mg/l) Nasoenteric tube feeding < 24 hrs after randomization vs oral diet after 72 hrs with tube feeding if not tolerated Primary outcome composite of major infection or death during 6 months follow-up Bakker OJ. New Engl J Med 2014;371:

17 Caloric intake Bakker OJ. New Engl J Med 2014;371:

18 Early enteral feeding in predicted severe acute pancreatitis 30 22,5 Early EN On demand P = 0.76 P = 0.87 P = , Major infection / Death Major infection Mortality In the on-demand group 69% tolerated an oral diet Bakker OJ. New Engl J Med 2014;371:

19 Endoscopic retrograde cholangiography Early ERC not effective in patients with predicted mild pancreatitis Emergency ERC with sphincterotomy < 24 hrs is indicated in case of concomitant cholangitis Routine early ERC with sphincterotomy in predicted severe biliary pancreatitis is controversial

20 Beyond the early phase Imaging Infected necrotising pancreatitis

21 CECT-scan In the first 3-4 days unreliable for detection of extent of necrosis or presence of collections Urgent CECT only in case of suspected abdominal catastrophe including perforation, bleeding and ischemia If a patient does not improve after 5-7 days CECT is indicated to determine the presence and extent of necrosis

22 Revised Atlanta criteria Interstitial oedematous pancreatitis Necrotising pancreatitis parenchymal peripancreatic both Acute pancreatic fluid collections Banks. PA. Gut 2013;62:

23 Complications of interstitial oedematous pancreatitis Rare Usually after > 4 weeks Well circumscribed (round/ oval) Homogenous fluid density Well defined wall Pancreatic pseudocyst

24 Necrotizing pancreatitis Only peripancreatic Both Only pancreatic Acute necrotic collections Heterogenous with varying density No definable wall

25 Walled-off necrosis Encapsulation of necrotic tissue Usually around 4-6 weeks Intervention only in case of infection! Consider intervention after 6-8 weeks in case of mechanical obstruction or failure to thrive Heterogenous with liquid/non-liquid density - well defined complete wall

26 Walled-off necrosis

27 Outcome acute collections Acute interstitial pancreatitis (36) Acute peripancreatic fluid collection (N = 8) Pseudocyst (N = 1) Acute pancreatitis N = died 21 resolved collection Acute necrotic pancreatitis (153) Acute necrotic collection (143) WON (N = 84) 8 died 53 intervention 23 conservative Manrai M. Ann Surg 2018;267:

28 CECT-scan infected necrosis Extraluminal gas in pancreas and peripancreatic tissues Positive gram stain/culture after FNA

29 Infected necrotizing pancreatitis Acute necrotic collections or walled-off necrosis become infected in one third of patients With proven infection or high clinical suspicion antibiotics are indicated Although antibiotics only may be successful, further intervention (catheter drainage / necrosectomy) is usually necessary

30 Intervention Delay intervention until stage of WON Catheter drainage followed by necrosectomy if clinically indicated Endosonography-guided transgastric necrosectomy may be the preferred technique

31 Step-up approach Multicentre randomized trial (N = 88) Necrotizing pancreatitis with confirmed or suspected infection Primary open necrosectomy vs step-up approach (percutaneous drainage, minimally invasive retroperitoneal necrosectomy) Primary outcome composite of major complications or death van Santvoort HC. N Engl J Med 2010;362:

32 Step-up approach Open necrosectomy Step-up approach P = P = P = 0.70 P = , , Major complicateon / Death New MOF Mortality New onset diabetes van Santvoort HC. N Engl J Med 2010;362:

33 Catheter drainage VARD

34 Endoscopic necrosectomy Multicentre randomized trial (N = 98) Necrotizing pancreatitis with confirmed or suspected infection and indication for invasive intervention Endoscopic (transluminal drainage, necrosectomy) versus surgical (percutaneous catheter drainage, VARD) Primary outcome composite of major complications or death (6 M) van Brunschot S. Lancet 2018

35 Endoscopic necrosectomy 50 37,5 43 Endoscopic Surgical P = 0.88 P = , Major complicateon / Death Mortality Decreased incidence of pancreatic fistula and decreased hospital LOS van Brunschot S. Lancet 2018

36 Candida infection Hall AM. Crit Care 2013;17:R49

37 Candida infection Hall AM. Crit Care 2013;17:R49

38 Local complications Acute peripancreatic fluid collection Pancreatic pseudocyst Acute necrotic collection Walled-off necrosis Gastric outlet dysfunction Splenic and portal vein thrombosis Colonic necrosis

39 Aftercare Prevention of recurrence Exocrine and endocrine insufficiency (19-80%)

40 Prevention of recurrence In total 17-22% recurrence of pancreatitis and 8-16% chronic pancreatitis Refrain from alcohol and cigarettes Cholecystectomy (severe pancreatitis - wait until recovery or 6 weeks after discharge, mild pancreatitis - during same hospital admission) % Same hospital admission Interval after 4 weeks Mild pancreatitis 5 0 Gallstone related complications Recurrent pancreatitis

41 Conclusion

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