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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

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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

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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

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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)

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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

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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

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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

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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

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Prognosis Predictor Scoring Systems

• Ranson’s Criteria

• BISAP Score
  • 0-2 points – low mortality
  • 3-5 points – high mortality

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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

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Complications

• Necrosis
• Pseudocyst
• Splanchnic venous thrombosis

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References

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