Pancreatitis, Acute

Essentials of Diagnosis

• Abrupt onset of deep epigastric pain, often with radiation to the back

• Nausea, vomiting, sweating, weakness, fever

• Abdominal tenderness and distention

• Leukocytosis, elevated serum amylase, elevated serum lipase

• History of previous episodes, often related to alcohol intake

General Considerations

• Most often due to passed gallstone, usually < 5 mm in diameter, or to heavy alcohol intake

• Rarely, may be the initial manifestation of a pancreatic or ampullary neoplasm

• The pathogenesis may include edema or obstruction of the ampulla of Vater, bile reflux into pancreatic ducts, or direct injury of the pancreatic acinar cells

• Annual incidence of acute pancreatitis ranges from 13 to 45 per 100,000 population and has increased since 1990

Symptoms and Signs

• There may be a history of alcohol intake or a heavy meal immediately preceding the attack, or a history of milder similar episodes or biliary pain in the past

• An international classification of the severity of acute pancreatitis has been proposed

  • Mild: absence of pancreatic or peripancreatic necrosis and organ failure

  • Moderate: presence of sterile (peri)pancreatic necrosis and/or transient (< 48 hours) organ failure using the sequential organ failure assessment (SOFA) score

  • Severe: presence of infected (peri)pancreatic necrosis or persistent (≥ 48 hours) organ failure

  • Critical: presence of infected (peri)pancreatic necrosis and persistent organ failure

Pain

• Severe, steady, boring epigastric pain, generally abrupt in onset; usually radiates into the back but may radiate to the right or left

• Often made worse by walking and lying and better by sitting and leaning forward

• The upper abdomen is tender, most often without guarding, rigidity, or rebound

• There may be distention and absent bowel sounds from paralytic ileus

• Nausea and vomiting

• Weakness, sweating, and anxiety in severe attacks

• Fever of 38.4–39.0°C, tachycardia, hypotension (even shock), pallor, and cool clammy skin are present in severe cases

• Mild jaundice may be seen

• Occasionally, an upper abdominal mass may be palpated

• Acute kidney injury (usually prerenal) may occur early in the course

Differential Diagnosis

• Acute cholecystitis

• Acutely perforated duodenal ulcer

• Acute intestinal obstruction

• Leaking aortic aneurysm

• Renal colic and acute mesenteric ischemia

Laboratory Tests

• Serum amylase and lipase increase, usually > 3 times normal, within 24 h in 90% of cases; lipase remains elevated longer than amylase and is slightly more accurate for diagnosis

• Leukocytosis (10,000–30,000/mcL), proteinuria, granular casts, glycosuria (10–20% of cases), hyperglycemia, and hyperbilirubinemia may be present

• Blood urea nitrogen (BUN) and serum alkaline phosphatase may be elevated and coagulation tests abnormal

• An early rise in serum levels of neutrophil gelatinase-associated lipocalin has also been proposed as a marker of severe acute pancreatitis

• An elevated serum creatinine level (> 1.8 mg/dL [149.94 mcmol/L]) at 48 hours is associated with the development of pancreatic necrosis

• A serum alanine aminotransferase level of more than 150 units/L (3 mkat/L) suggests biliary pancreatitis

• Hypocalcemia correlates with severity of disease; levels < 7 mg/dL (1.75 mmol/L) (when serum albumin is normal) are associated with tetany

• Early hemoconcentration, hematocrit value above 44%, predicts pancreatic necrosis

• An elevated C-reactive protein concentration (> 150 mg/dL [1500 mg/L]) after 48 h suggests severe disease

• The fluid amylase content is high in ascites or left-sided pleural effusions

Imaging Studies

• Plain abdominal radiographs may show

  • Gallstones (if calcified)

  • A "sentinel loop" (a segment of air-filled left upper quadrant small intestine)

  • The "colon cutoff sign" (a gas-filled segment of transverse colon abruptly ending at the pancreatic inflammation)

  • Focal linear atelectasis of the lower lobe of the lungs with or without pleural effusion

• Ultrasonography

  • Often unhelpful for the diagnosis of acute pancreatitis

  • However, it may identify gallstones

• CT scan

  • Can demonstrate an enlarged pancreas and pseudocysts

  • Can differentiate pancreatitis from other possible intra-abdominal catastrophes

  • Can provide initial assessment of prognosis

• Dynamic intravenous contrast-enhanced CT

  • Of particular value after the first 3 days of severe disease to identify necrotizing pancreatitis and assess prognosis

  • Avoid intravenous contrast when the serum creatinine level is > 1.5 mg/dL (124.95 mcmol/L); order MRI instead

• Endoscopic ultrasonography is useful for occult biliary disease (eg, small stones, sludge)

Diagnostic Procedures

• ECG may show ST–T wave changes

• CT-guided needle aspiration of necrotizing pancreatitis may diagnose infection

• Endoscopic retrograde cholangiopancreatography (ERCP) is generally not indicated after a first attack unless there is associated cholangitis or jaundice

• However, aspiration of bile for crystal analysis may confirm microlithiasis

• The Ranson criteria for severity of acute pancreatitis are outlined in Table 16–10

Medications

• Meperidine

  • Up to 100–150 mg every 3–4 hours intramuscularly as necessary for pain

  • Reduce dose with severe hepatic or kidney dysfunction

  • Given potential side effects, morphine may be preferable alternative

• Give nothing by mouth until the patient is largely free of pain and has bowel sounds

• Begin with clear liquids and gradually advance to a low-fat diet, guided by the patient's tolerance and by absence of pain

• For mild pancreatitis

  • Early fluid resuscitation (one-third of the total 72-hour fluid volume administered within 24 hours of presentation, 250–500 mL/h initially) may reduce the frequency of systemic inflammatory response syndrome and organ failure

  • Lactated Ringer solution may be preferable to normal saline

  • However, overly aggressive fluid resuscitation may lead to morbidity as well

• For severe pancreatitis, large amounts of intravenous fluids are needed to maintain intravascular volume

• Give calcium gluconate intravenously for hypocalcemia with tetany

• Infusions of fresh frozen plasma or serum albumin may be needed for coagulopathy or hypoalbuminemia

• If shock persists after adequate volume replacement (including packed red cells), vasopressors may be required

• Enteral nutrition via a nasogastric or nasojejunal tube is preferable to parenteral nutrition in patients who will otherwise be without oral nutrition for at least 7–10 days but it may not be tolerated in some patients with an ileus and does not reduce the rates of infection and death compared with the introduction of an oral diet after 72 hours

• Parenteral nutrition (including lipids) should be considered in patients who have severe pancreatitis and an ileus

• Imipenem (500 mg every 6 hours intravenously), the combination of ciprofloxacin (750 mg twice daily intravenously) and metronidazole (500 mg three times daily intravenously or three times daily orally), or possibly cefuroxime (1.5 g three times daily intravenously and then 250 mg twice daily orally), given for 14 days for sterile necrotizing pancreatitis, may reduce the risk of pancreatic infection

• The role of intravenous somatostatin is uncertain, but octreotide is not beneficial

Surgery

• For mild pancreatitis with cholelithiasis, cholecystectomy or cholecystotomy may be justified

• Infected pancreatic necrosis is an absolute indication for debridement

• Biliary sphincterotomy

  • Used to treat recurrent acute pancreatitis attributable to pancreatic sphincter of Oddi dysfunction

  • As effective as combined biliary and pancreatic sphincterotomy in reducing frequency of recurrent acute pancreatitis

  • However, chronic pancreatitis may still develop in treated patients

• Necrosectomy may improve survival of patients with necrotizing pancreatitis and clinical deterioration with multiorgan failure or lack of resolution by 4 weeks

Therapeutic Procedures

• The pancreatic rest program includes

  • Nothing by mouth

  • Bed rest

  • Nasogastric suction for vomiting, moderately severe pain, or abdominal distention

• ERCP with endoscopic sphincterotomy and stone extraction is indicated when severe pancreatitis results from choledocholithiasis, particularly if jaundice (serum total bilirubin > 5 mg/dL [85.5 mcmol/L]) or cholangitis is present

• A "step-up" approach involves nonsurgical drainage of walled-off pancreatic necrosis under radiologic guidance first, with open surgical necrosectomy reserved for patients who fail to improve. This approach has been shown to reduce mortality in selected patients with necrotizing pancreatitis and confirmed or suspected secondary infection

• Endoscopic (transgastric or transduodenal) drainage combined with percutaneous drainage and in some cases laparoscopic guidance (video-assisted retroperitoneal debridement [VARD]) are additional options

• Treatment is labor intensive, and multiple procedures are often required

• Endoscopic or surgical interventions may be required for chronic disconnected pancreatic duct syndrome

Follow-Up

• Monitor severely ill patients closely

  • White blood cell count

  • Hematocrit

  • Serum electrolytes

  • Serum calcium

  • Serum creatinine

  • BUN

  • Serum aspartate aminotransferase and lactate dehydrogenase (LD)

  • Arterial blood gases

• Cultures of blood, urine, sputum, and pleural effusion (if present) and needle aspirations of pancreatic necrosis (with CT guidance) should be obtained

• Following recovery from gallstone-related acute pancreatitis, laparoscopic cholecystectomy is generally performed, although endoscopic sphincterotomy alone may be done

Complications

• Acute tubular necrosis

• Necrotizing pancreatitis and infected pancreatic necrosis

• Acute respiratory distress syndrome (ARDS); cardiac dysfunction may be superimposed

• Pancreatic abscess may develop after 6 or more weeks; it requires prompt percutaneous or surgical drainage

• Treat pancreatic infections with imipenem, 500 mg every 8 hours intravenously

• Pseudocysts < 6 cm in diameter often resolve spontaneously

  • They are multiple in 14% of cases

  • They may become secondarily infected and need drainage

  • Drainage may also help persisting pain or pancreatitis

• Pancreatic ascites may present after recovery from acute pancreatitis with absence of frank abdominal pain. Marked elevations in the ascitic protein (> 3 g/dL) and amylase (> 1000 units/L [20 mkat/L]) levels are typical

• Portosplenomesenteric venous thrombosis frequently develops in patients with necrotizing acute pancreatitis but rarely leads to complications

• Chronic pancreatitis develops in about 10% of cases

• Permanent diabetes mellitus and exocrine pancreatic insufficiency occur uncommonly after a single acute episode

Prognosis

RANSON CRITERIA FOR SEVERITY OF ACUTE PANCREATITIS

• Help assess disease severity

• When three or more of the following are present on admission, a severe course complicated by pancreatic necrosis can be predicted with a sensitivity of 60–80% (Table 16–10)

  • Age older than 55 years

  • White blood cell count > 16,000/mcL

  • Blood glucose > 200 mg/dL

  • Serum LD > 350 units/L

  • AST > 250 units/L

• Development of the following in the first 48 h indicates a worsening prognosis

  • Hematocrit drop of more than 10 percentage points

  • BUN rise > 5 mg/dL

  • Arterial PO₂ of < 60 mm Hg

  • Serum calcium of < 8 mg/dL

  • Base deficit > 4 mEq/L

  • Estimated fluid sequestration of > 6 L

• Mortality rates correlate with the number of criteria present on admission and within the first 48 h

  • 0–2, 1%

  • 3–4, 16%

  • 5–6, 40%

  • 7–8, 100%

• Severity can also be assessed using the Acute Physiology and Chronic Health (APACHE) II or III scoring system as well as the CT scan index (Table 16–11)

• The Pancreatitis Activity Scoring System (PASS), a dynamic assessment instrument, includes five components:

  • Organ failure

  • Systemic inflammatory response syndrome

  • Abdominal pain

  • Opioid requirement

  • Intolerance of oral intake

• Multiorgan failure that persists beyond the first 48 hours is associated with a mortality rate over 50%

When to Admit

• Nearly all patients with severe pancreatitis