#65 – Pancreatitis



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Epidemiology

  • 13-45 per 100,000 person incidence in the US
  • Most common GI cause of hospital admission in the US
    • > 300,000 per year
    • Average 4-day stay with cost > $6000/case
  • Equal gender representation across the lifespan
    • Alcohol pancreatitis more common in men
  • 2-3 fold higher rates in African Americans

Risk Factors and Etiologies

  • Gallstones
    • 40-70% of cases
      • Only 3-7% of patients with gallstones develop pancreatitis
    • Two theorized mechanisms
      • Reflux of bile into the pancreatic duct
      • Obstruction at the ampulla
    • Magic number is 5mm
      • Small enough to pass through cystic duct, but still get obstructed at ampulla
  • Alcohol
    • 25-35% of cases
    • Interesting data to show that it is not just alcohol that causes pancreatitis
      • 5 out of 100,00 patents with alcohol abuse develop pancreatitis
    • Several mechanisms theorized
      • Sensitization of acinar cell to CCK-induced activation of zymogens
      • Potentiation of the effect of CCK
      • Generation of toxic metabolites
      • Sensitization of the pancreas to toxic insults
      • Activation of pancreatic stellate cells to increase production of matrix proteins
  • Idiopathic (genetic)
    • 15-25% of patients with pancreatitis have no identifiable pathologic cause
    • These cases are largely theorized to have complex genetic risk profiles
  • Hypertriglyceridemia
    • 1-14% of cases
    • > 1000 mg/dL increases risk
  • Post-ERCP
    • 3% of patients undergoing diagnostic ERCP
    • 5% of patients undergoing therapeutic ERCP
    • 25% of patients undergoing sphincter of Oddi measurements
  • Medications
    • < 5% of cases
    • Classification system (Ia, Ib, II, III, IV)
    • Prognosis is excellent and mortality is very low
  • Obesity
  • Smoking
  • Diabetes

Pathogenesis

  • Pancreatic enzymes synthesis continues while secretion is slowed or halted
  • HIT #1 –  Intraacinar activation of proteolytic enzymes (trypsin)
    • Cascade of enzyme release and activation then occurs
    • Ultimately, causes autodigestion of the pancreas
  • HIT #2 – Microcirculatory injury
    • Damage to the pancreas via autodigestion leads to vasoconstriction, decreased oxygenation, and progressive ischemia
      • Leads to edema and further decreased secretion of enzymes
  • HIT #3 – Leukocyte infiltration, cytokine release, and oxidative stress
    • Leads to widespread inflammation and induce thrombosis and hemorrhage
    • Ultimately, causes necrosis
  • Two main classifications
    • Interstitial pancreatitis – blood supply is maintained
    • Necrotizing pancreatitis – blood supply is affected

Signs and Symptoms

  • History
    • Epigastric pain
      • May radiate to the back
      • May radiate to the right shoulder
        • Kehr’s sign
    • Nausea
    • Vomiting
    • Dyspneic
      • Severe disease can cause diaphragmatic irritation and pleural effusions
  • Physical Examination
    • Fever
    • Tachycardia
    • Epigastric tenderness
    • Abdominal distention
    • Hypoactive bowel sounds
    • Jaundiced
    • Abdominal ecchymosis (necrotizing disease)
      • Cullen’ sign – umbilical
      • Grey Turner’s sign – flank
      • Fox’s sign – thigh (parallel but inferior to inguinal ligament)

Laboratory Studies

  • Serum amylase
    • Rises within 6 hours, returns to normal in 3-5 days
    • Should not be used (sensitivity 67-83%, specificity 85-98%)
      • Short-half life (10 hours)
        • Patients presenting > 24 hours after onset can have normal amylase
      • Miss up to 20% of cases of alcohol pancreatitis
        • Due to inability of parenchyma to produce amylase
      • Miss up to 50% of cases of hypertriglyceridemia
        • Triglycerides interfere with assay
  • Serum lipase
    • Sensitivity 85-100%
    • Rises 4-8 hours, peaks at 24 hours, returns to normal in 8-14 days
  • LFTs
    • Evaluate for cholestatic elevations (ALP, bilirubin, GGT)
  • BMP
    • Need glucose, BUN, and calcium for some of the risk calculators
  • CBC
    • Leukocytosis often is present and helps grade severity
    • May show hemoconcentration due to volume depletion

Imaging Studies

  • Ultrasound
    • Often the quickest and easiest study to obtain in the ED
    • Can evaluate gallbladder pathology, stones, and peripancreatic fluid
    • Ileus can obscure imaging due to gas overlying the pancreas
  • CT
    • Better detail and can evaluate more structures
  • MRI
    • Higher sensitivity in early disease
    • Longer to obtain
  • Revised Atlanta Criteria
    • Six CT morphological features
    • Interstitial edema
      • Parenchymal enhancement by IV contrast
    • Necrotizing findings
      • Lack of parenchymal enhancement
      • Peripancreatic fluid collection or walled-off necrosis
    • Acute peripancreatic fluid collection
      • Homogenous fluid collection
      • Confined to normal peripancreatic fascial planes
      • No definable encapsulating wall
      • Adjacent to pancreas (no intrapancreatic extension)
    • Pancreatic pseudocyst
      • Well-circumscribed, well-defined wall with homogenous fluid density
      • No non-liquid component
    • Acute necrotic collection
      • Heterogenous with non-liquid density of varying degrees
      • No definable wall
      • Intra-, or extra-pancreatic in location
    • Walled-off necrosis
      • Heterogenous with liquid and non-liquid densities
      • Well-defined wall that is completely encapsulated
      • Intra-, or extra-pancreatic in location

Diagnosis

  • Need 2 of the following 3 criteria:
    • Acute onset of persistent, severe, epigastric pain
    • Elevation of amylase or lipase > 3x ULN
    • Radiographic findings on imaging

Classification of Severity

  • Mild
    • Absence of organ failure or local/systemic complications
  • Moderately severe
    • Transient organ failure (resolves with 48 hours) and/or systemic complications without persistent organ failure
  • Severe
    • Persistent organ failure

Prognosis Predictor Scoring Systems

  • Ranson’s Criteria
  • BISAP Score
    • 0-2 points – low mortality
    • 3-5 points – high mortality

Management

  • Patients with mild pancreatitis can be admitted to floor/wards
  • Patients with moderately severe or severe should be admitted to ICU
  • Fluid resuscitation
    • 5-10 mL/kg/hour with crystalloid
      • Careful, using LR in patients with hypercalcemic induced pancreatitis
    • Bolus 20 ml/kg over 30 minutes if hypotensive/tachycardic
    • Adjust using goal-directed metrics even 6 hours for first 24 hours-48 hours
      • BUN, H/H, MAP (65-85 mmHg), HR (< 120bpm), UOP (>0.5 mL/kg/hr)
  • Pain control
    • Opioids are safe and PCA can work well
      • Fentanyl has better safety profile
        • 20-50 mcg with 10-min lockout
  • Nutrition
    • Can reintroduce within 24 hours if no nausea, vomiting, and decreasing pain and inflammatory markers
      • Start with low-residue, low fat, soft diet and advance as tolerated
    • Supplemental nutrition generally needed for moderately severe and severe cases, or if unable to tolerate oral nutrition within 5 days
      • Enteral > parental with placement of jejunal feeding tube beyond the ligament of Treitz
        • Helps prevent bacterial translocation
      • Parenteral is indicated if nutritional goals are not achieved with 48-72 hours due to pain or intolerance
      • Consult your hospital nutritional team and/or dietician for help
  • Antibiotics
    • No evidence to support prophylactic antibiotics
      • Most infected necroses will occur late in clinical course (5-10 days after admission)
  • Treat underlying causes
    • Gallstone pancreatitis
      • ERCP should be performed within 24 hours of admission
      • Cholecystectomy should be performed within 7 days and often during same hospitalization
    • Hypertriglyceridemia
      • Therapeutic plasma exchange and insulin therapy

Complications

  • Necrosis
  • Pseudocyst
  • Splanchnic venous thrombosis


References

  1. Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013; 144(6):1252-61. [PDF]
  2. Conwell DL, Banks PA, Greenberger NJ. Acute and Chronic Pancreatitis. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. eds. Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill;
  3. Mechanisms of alcoholic pancreatitis. Proceedings of a conference. Chicago, Illinois, USA, November 2002. Pancreas. 2003; 27(4):281-355. [pubmed]
  4. Nawaz H, Koutroumpakis E, Easler J, et al. Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis. Am J Gastroenterol. 2015; 110(10):1497-503. [pubmed]
  5. Scherer J, Singh VP, Pitchumoni CS, Yadav D. Issues in hypertriglyceridemic pancreatitis: an update. J Clin Gastroenterol. 2014; 48(3):195-203. [PDF]
  6. Kahaleh M, Freeman M. Prevention and management of post-endoscopic retrograde cholangiopancreatography complications. Clin Endosc. 2012; 45(3):305-12. [PDF]
  7. Lankisch PG, Dröge M, Gottesleben F. Drug induced acute pancreatitis: incidence and severity. Gut. 1995; 37(4):565-7. [PDF]
  8. Forsmark CE, Swaroop Vege S, Wilcox CM. Acute Pancreatitis N Engl J Med. 2016; 375(20):1972-1981.
  9. Yadav D, Agarwal N, Pitchumoni CS. A critical evaluation of laboratory tests in acute pancreatitis. Am J Gastroenterol. 2002; 97(6):1309-18. [pubmed]
  10. Wu BU, Johannes RS, Sun X, Tabak Y, Conwell DL, Banks PA. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008; 57(12):1698-703. [pubmed]
  11. Vege SS, DiMagno MJ, Forsmark CE, Martel M, Barkun AN. Initial Medical Treatment of Acute Pancreatitis: American Gastroenterological Association Institute Technical Review. Gastroenterology. 2018; 154(4):1103-1139. [pubmed]
  12. Basurto Ona X, Rigau Comas D, Urrútia G. Opioids for acute pancreatitis pain. Cochrane Database Syst Rev. 2013; [pubmed]
  13. Casaer MP, Mesotten D, Hermans G, et al. Early versus late parenteral nutrition in critically ill adults. N Engl J Med. 2011; 365(6):506-17. [pubmed]
  14. Kutsogiannis J, Alberda C, Gramlich L, et al. Early use of supplemental parenteral nutrition in critically ill patients: results of an international multicenter observational study. Crit Care Med. 2011; 39(12):2691-9. [pubmed]
  15. Aboulian A, Chan T, Yaghoubian A, et al. Early cholecystectomy safely decreases hospital stay in patients with mild gallstone pancreatitis: a randomized prospective study. Ann Surg. 2010; 251(4):615-9. [pubmed]
  16. Uhl W, Müller CA, Krähenbühl L, Schmid SW, Schölzel S, Büchler MW. Acute gallstone pancreatitis: timing of laparoscopic cholecystectomy in mild and severe disease. Surg Endosc. 1999; 13(11):1070-6. [pubmed]
  17. Ipe TS, Pham HP, Williams LA 3rd. Critical updates in the 7 edition of the American Society for Apheresis guidelines. J Clin Apher. 2018; 33(1):78-94. [pubmed]

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