Ashley Duckett, MD Theresa Cuoco, MD, FACP Acute Pancreatitis Ashley Duckett, MD Theresa Cuoco, MD, FACP

Objectives Identify clinical presentation and etiologies of acute pancreatitis Recognize the importance of severity of pancreatitis in determining management and outcomes Understand the indications for imaging and antibiotics in acute pancreatitis

Key Messages Early aggressive hydration is critical in the management of acute pancreatitis. Imaging with contrasted CT or MRI is indicated at 48-72 hours in patients with severe disease. Early enteral nutrition improves outcomes in patients with severe pancreatitis. Severity scores can be used to triage patients at risk for complications.

Clinical presentation Abdominal pain, distention Nausea/vomiting (90%) Fever, tachycardia, shock, coma Dyspnea (pleural effusion) Shallow respirations (diaphragmatic irritation) Jaundice Grey-Turner’s/Cullen’s 1% - intraabdominal hemorrhage

Etiologies Gallstones- 35-40% (increased ALT >150 is 50% sensitive and 96% specific) *women Alcohol – 30% *men Hypertriglyceridemia Hypercalcemia Post-ERCP -3% of diagnostic, 25% if SOD studies Drugs – direct toxic, immunologic, ischemic causes – cocaine, HCTZ Genetic mutations Trauma Infection – Viruses (mumps, hep B, CMV, HIV), Bacteria (mycoplasma, legionella, salmonella), fungi, parasites Idiopathic -15-20% Autoimmune (although usually presents mimicking neoplasm) Scorpion bite SOD dysfunction? Pancreatic divisum?

Pathophysiology Activation of trypsin in acinar cells Activating multiple pancreatic digestive enzymes (synthesized but not secreted) Leak into interstitial space and systemic circulation Intrapancreatic Inflammation Mediated by cytokines/inflammatory markers SIRS Extrapancreatic Inflammation ARDS Multiple organ failure (MOF) Respiratory, cardiovascular, renal

Diagnosis Requires 2 of the following 3 features Characteristic abdominal pain Epigastric, band-like radiating to back, assoc n/v Amylase and/or lipase >/= 3 times the upper limit Amylase rises in 6-12 hrs, elevated 3-5 days Lipase sensitivity 85-100%; more specific than amylase Characteristic CECT (contrast enhanced CT) findings (or MRI/US) Edema, peripancreatic fat stranding, necrosis, calcifications, pancreatic heterogeneity

Imaging Plain XR – unremarkable or have “sentinel loop” (localized ileus) or “colon cutoff sign” in severe disease CXR – pleural effusion suggests increased risk of complications Abd ultrasound: diffuse, hypoechoic pancreas, useful for gallstones, not good for necrosis CT scan – useful for complications and for severity assessment When to CT? indicated if need to assess for necrosis (severe disease) at 48-72 hours Oral and IV contrast preferred (to diagnose necrosis, calcifications, stones, mass) MRCP – best for delineating fluid collections, necrosis, ducts, looking for choledocholithiasis

Management Determine etiology – history, LFTs, TGs, calcium, abdominal ultrasound for stones Determine severity and send severe to ICU FLUIDS FLUIDS FLUIDS – Initial bolus, then 250-300cc/hr x 48 hours if cardiac fx normal Increasing BUN at 24 hrs predicts mortality Monitor glucose and lytes (Ca, Mg) No daily amylase/lipase; no correlation with severity Pain management Nutrition – start oral feeds when pain improving, no ileus in mild dz

Nutrition Need for nutrition and pancreatic rest in severe pancreatitis or anyone NPO > 5 days Early enteral nutrition (at 24-48 hrs) reduces mortality, multi-system organ failure, infections and need for operative interventions compared to TPN Maintains intestinal barrier, prevents translocation High protein, low fat formula

Antibiotics ACG – prophylactic antibiotics not recommended AGA – abx should be restricted to pts with >30% pancreatic necrosis by CT and should be used for less than 14 days Meropenem or imipenem are drugs of choice CT guided aspiration/culture recommended if infected pancreatic necrosis is suspected (fevers, sepsis, increasing WBC)

Classification of Acute Pancreatitis Interstitial edematous Acute inflammation of pancreatic parenchyma and peripancreatic tissue Necrotizing Acute Pancreatitis 5-10% of patients Pancreatic or peripancreatic necrosis Appears as non-enhancing area Early CECT may underestimate (wait 48-72h)

Severity of Pancreatitis Mild Acute No organ failure, local or systemic complications Moderately Severe Transient organ failure (OF) <48h Local or systemic complications w/o persistent OF Severe Acute Persistent organ failure (>48h) Mortality ~36-50%; higher w infected necrosis

Severity scores Most cases mild, 15-25% severe Depends on presence and duration of organ failure Early risk stratification (median time to ICU transfer is 24 hours after admission) APACHE II most widely used – score >8=severe BISAP – simple, can be done early BUN, AMS, SIRS, Age>60, pleural effusion >3 points indicates increased risk of death Ranson’s criteria

Ranson’s Criteria At admission At 48 hrs out Age > 55 WBC > 16 Glu > 200 AST > 250 LDH > 350 Ca < 8 HCT fall > 10% PO2 < 60 BUN increase > 5 Base deficit > 4 mEq/L Sequestration of fluids > 6L Criteria Met Mortality 0-2 2% 3-4 15% 5-6 40% 7-8 100%

Complications Pancreatic necrosis – becomes infected in about 30%; usually monomicrobial (Ecoli, Pseudomonas, Kleb) Abscesses Pseudocysts -Drainage prior to maturation (6 wks) can lead to complications Splenic vein thrombosis (up to 19% of pts) Anticoagulation may be needed for complications Abdominal compartment syndrome ARDS, shock, renal failure, GI bleeding

Definitions of Pancreatic and Peripancreatic Fluid Collections APFC: Acute Peripancreatic Fluid Collection Assoc w intersitial panc; no necrosis Homogenous; no definable wall; adjac to pancreas Pancreatic Pseudocyst Well circumscribed, homogenous, with wall Maturation usually >4 weeks after acute panc ANC: Acute Necrotic Collection Only in setting of necrotizing panc Heterogenous, no wall, intra and/or extra pancreatic WON: Walled Off Necrosis Heterogenous, well defined wall, intra/extra Maturation >4 weeks after acute necrotizing panc

Gallstone pancreatitis – early ERCP or surgery? Early ERCP or surgery to remove bile duct stones may decrease severity of pancreatitis ERCP within 72 hours in pts with cholangitis OR concern for stone (stone on imaging, dilated CBD, jaundice, rising LFTs) All patients with gallstone panc should have cholecystectomy 25-30% risk of recurrent panc, cholecystitis or cholangitis in <18 wks Recent retrospective of mild gallstone panc who had lap chole within 48 hrs of admission No increase in morbidity or mortality Decreased hospital stay and ERCP Consider early consult in appropriate patients

References Banks P et al. Practice Guidelines in Acute Pancreatitis. Am J Gastroenterol 2006; 101:2379-2400 Banks P et al. Classification of acute pancreatitis-2012:revision of the Atlanta classification and definitions by international consensus. Gut 2013; 62: 102-111. Al-Omran M et al. Enteral versus Parenteral Nutrition for Acute Pancreatitis (Review). Cochrane Database of Systematic Reviews 2010, Issue1 Falor et al. Early Laparoscopic Cholecystectomy for Mild Gallstone Pancreatitis. Arch Surg 147: Nov 2012 Van Santvoort et al. Early Endoscopic Retrograde Cholangiopancreatography in Predicted Severe Acute Biliary Pancreatitis: A Prospective Multicenter Study. Annals of Surgery. 250 (1); July 2009 Wu, Bechien. Prognosis in Acute Pancreatitis. CMAJ: 183 (6); April 2011