acute pancreatitis

Etiology

• common causes (80-90% of cases)
  • alcoholism
  • gallstone disease (most common)
    • biliary sludge or microlithiasis
• uncommon causes
  • abdominal trauma
    • including trauma caused by ERCP
  • post-operative, especially coronary artery bypass (CABG)
  • infections
    • viral: mumps, hepatitis B, coxsackie B, HIV
    • bacterial: Mycoplasma, Campylobacter
    • parasitic: ascaris, toxoplasmosis
  • hyperlipidemia, hypertriglyceridemia
    • serum triglycerides > 500 mg/dL generally accepted threshold for increased risk for acute pancreatitis
    • serum triglycerides > 1000 mg/dL; > 2000 mg/dL
    • baseline risk 3 per 10,000 with serum triglycerides < 90 mg/dL
    • risk increases 4-fold to 12 per 10,000 with serum triglycerides of 440 mg/dL
  • hypercalcemia
  • pharmaceutical agents (see causes of acute pancreatitis)
  • vascular
    • ischemia
    • vasculitis
  • biliary duct & pancreatic duct abnormalities
• risk factors for idiopathic pancreatitis*
  • smoking & other environmental toxins
  • obesity
  • diabetes mellitus

* idiopathic acute pancreatitis increases with age

Epidemiology

• hospital admissions for acute pancreatitis have increased by at least 20% 2006-2016
  • large increases in incidence in pediatric populations
  • increased risk of pancreatitis tracks with the worldwide obesity epidemic and increasing rates of gallstones

Pathology

• trypsinogen activation to trypsin
• release of intracellular lysosomal enzymes
• disruption of zymogen granules by refluxed pancreatic juice or duodenal obstruction
• trypsin activation of phospholipases, elastases, kallikreins, & other mediators
• neutrophil migration & release of inflammatory cytokines
• bacterial invasion with localized sepsis
• pancreatic necrosis (most important prognostic factor)
• multiorgan failure

Genetics

genetic predispositions

• mutations in PRSS1, SPINK1, CFTR, CTRC, CASR, CLDN2
• these mutations may interact with other causal factors
  • claudin-2 (CLDN2) mutations synergistic with alcohol

Clinical manifestations

• acute onset upper abdominal pain, rebound tenderness suggests complications
  • pain may radiate to back
• low grade fever; high fever suggests complications (not a marker of severe disease)
• signs/symptoms of shock may be present
  • tachypnea
  • tachycardia
  • diaphoresis
• left-sided pleural effusion (minimal) may be present
• decreased bowel sounds secondary to paralytic ileus
  • absent bowel sounds suggests complications
• melena suggests complications
• uncommon findings
  • jaundice
  • abdominal distension
  • Grey-Turner sign: blueish discoloration of flanks
  • Cullen's sign:
    • blueish discoloration of periumbilical region
• most cases are mild, 20% of patients with severe disease

Diagnostic criteria

• at least 2 of 3 of the following
  • acute onset of upper abdominal pain
  • serum amulase or serum lipase increased >= 3-fold upper limit of normal
  • findings suggesting pancreatitis on ultrasound, CT or MRI

Laboratory

• serum amylase
  • > 3-4 times upper limit of reference interval suggests pancreatitis
  • serum amylase may be elevated in other conditions
    • acute cholecystitis
    • mesenteric thrombosis
    • intestinal obstruction,
    • perforated peptic ulcer
    • inflammation of the salivary gland - mumps
    • mild elevation with renal failure, intestinal ischemia, appendicitis, parotitis
  • does not correlate with prognosis (see Ranson's criteria)
  • may be normal
    • chronic pancreatitis with little functional pancreatic tissue
    • hyperlipidemic pancreatitis
  • pancreatic versus salivary amylase
• urine amylase is neither sensitive nor specific, but may be useful for excluding macroamylasemia
• serum lipase increases specificity
  • in connection with amylase
  • diagnosis requires serum lipase or serum amylase > 3-4 times upper limit of reference interval
• complete blood count (CBC)
  • may show leukocytosis (neutrophilia, not a marker of severe disease)
  • may show anemia or drop in hemoglobin/hematocrit
• serum chemistries
  • serum glucose
  • electrolytes
  • liver function tests
    • serum ALT (for Ranson criteria)
      • serum ALT > 3x upper limit of normal suggests gallstone pancreatitis
    • serum lactate dehydrogenase (for Ranson criteria)
  • urea nitrogen
    • serial urea nitrogen predicts disease severity
    • level > 20 mg/dL is poor prognostic indicator
    • best predictor of severe disease
  • elevated serum creatinine is poor prognostic indicator
  • serum Ca+2 (for Ranson criteria)
  • serum triglycerides (> 1000-2000 mg/dL)
• arterial blood gas
• serum procalcitonin can improve antibiotic stewardship
• testing in research phase
  • trypsin-activating polypeptide in urine
  • pancreatitis-associated protein in serum
• see ARUP consult

Diagnostic procedures

• endoscopic retrograde cholangiopancreatography (ERCP)
  • avoid in acute pancreatitis unless evidence of cholestasis or cholangitis or worsening of symptoms in the context of abnormal liver function tests
    • within 24 hours
    • avoid in 1st 72 hours unless cholangitis
  • evaluation of the pancreatic & common bile ducts
    • microlithiasis
    • stenosis of the sphincter of Oddi
    • traumatic pancreatitis
  • identification fluid collection prior to drainage
    • IL8 elevated in pancreatic fluid, but does not distinguish pancreatic carcinoma
  • sphincterotomy* if dilated common bile duct
  • pancreatic carcinoma
• culture of fine-needle aspiration fluid obtained under CT guidance (see radiology)

* sphincter of Oddi

Radiology

• abdominal ultrasound
  • all patients unless cause is obvious
  • preferred imaging modality to evaluate biliary cause of acute pancreatitis
  • gallbladder: gallstones or sludge suggests gallstone pancreatitis
  • size of common bile duct (biliary obstruction)
  • avoids risks of intravenous contrast material
  • endoscopic ultrasound or MRI if diagnosis unclear
• computed tomography (CT) of abdomen (IV contrast-enhanced)
  • indications
    • confirmation of diagnosis of acute pancreatitis (1st line)
      • serum lipase not diagnostic
    • diagnosis of complications or extensive pancreatic necrosis when the patient continues to deteriorate after 48 hours
    • inability to adequately visualize pancreas with ultrasound
  • IV contrast may constrict pancreatic & renal micro-circulation & worsen pancreatic injury
  • IV contrast puts patients at risk for contrast nephropathy
  • useful for assessing
    • size of pancreas
    • extent of pancreatic necrosis
    • fluid collections
  • CT-guided fine-needle aspiration for culture
  • peripancreatic edema resulting from pancreatic inflammation blurs the margins of the pancreas on CT (not a marker of severe pancreatitis)
• magnetic resonance imaging or CT required for diagnosis
• plain film of the abdomen (KUB)
  • perforated peptic ulcer
  • intestinal obstruction
  • non-specific signs
    • dilated loop of jejunum (sentinel loop)
    • dilated transverse colon (colon cutoff sign)

Complications

• pancreatic pseudocyst
  • most common complication
  • generally take at least 4 weeks to form
  • generally resolve spontaneously
  • if asymptomatic & not mucinous pseudosyt, requires no further testing or treatment
• repeated episodes may lead to chronic pancreatitis
• pancreatic necrosis (non-infectious) or phlegmon
  • may become infected
    • antibiotics essential for infected pancreatic necrosis
    • fine-needle aspiration should not be performed
  • diabetes mellitus if necrosis is extensive
• pancreatic abscess
• may increase risk of pancreatic cancer
• gastrointestinal hemorrhage
• splenic vein thrombosis
  • anticoagulation not recommended
• systemic inflammatory response syndrome
• pancreatitis may cause exudative ascites
• multiorgan failure
• mortality 5%

Management

• NPO (nothing by mouth) until pain subsides
  • consider oral feeding when pain has improved
• intravenous fluids to maintain circulatory volume & electrolyte balance
  • 10 mL/kg bolus only if hypovolemic, then 1.5 mL/kg/hour infusion with additional boluses if hypovolemic
  • formerly 20 mL/kg bolus followed by 3 mL/kg/hour superior to a lower rate in mild acute pancreatitis
  • most beneficial in 1st 12-24 hours, may be harmful after this
  • lactated Ringer's within 1st 24 hours may be associated with diminished risk of moderate-severe pancreatitis vs normal saline
• nasogastric tube (NGT) aspiration of stomach contents
• parenteral analgesics to relieve pain
  • meperidine (Demerol) 75-100 mg IM every 3-4 hours
• broad spectrum antibiotics
  • indications:
    • routine use not indicated unless evidence of extrapancreatic infection
    • severe biliary pancreatitis (cholangitis)
    • infected pancreatic necrosis
    • infected pseudocyst
  • antibiotics
    • imipenem-cilastatin, meropenem, doripenem, or piperacillin-tazobactam
    • metronidazole plus cefepime, ceftazidime, ciprofloxacin, or levofloxacin
    • ceftazidime, amikacin & metronidazole
    • ofloxacin & metronidazole
    • cefuroxime (alone)
    • add vancomycin (if MRSA suspected)
• surgery
  • most fluid collections resolve without intervention
  • abscess suspected
  • unstable patients with infected pancreatic necrosis despite appropriate antimicrobial therapy
  • diagnosis not clear
  • no relief with conservative measures
    • pancreatic pseudocyst
  • gallstone pancreatitis (see laboratory & radiology)
    • cholecystectomy after pancreatitis subsides
      • laparoscopic cholecystectomy within 48 hours of admission (before discharge) for mild pancreatitis
    • endoscopic papillotomy with stone extraction
  • traumatic pancreatitis
    • partial pancreatectomy distal to avulsed duct identified by ERCP for severe injury
    • drainage of cyst resulting from trauma
• newer, controversial or untested pharmaceuticals
  • octreotide
  • platelet-activating factor (PAF) antagonists
• nutritional support
  • resume feeding with low fat diet when asymptomatic
    • a low-fat diet started on admission results in hospital discharge ~5 days earlier than if feeding is delayed
  • enteral feeding within 72 hours if oral feeding not tolerated
    • elemental or peptide-based enteral feeding via nasojejunal route for moderate to severe disease
  • regular oral intake at 72-96 hours after admission is an acceptable strategy in patients with predicted severe acute pancreatitis
  • do not withhold oral feeding for persistent elevations of serum amylase or serum lipase
  • mild pancreatitis does not benefit from nutritional support
  • total parenteral nutrition
    • enteral feeding not feasible
    • may increase risk of sepsis
      • not an initial recommendation
    • monitor lipid intake
      • maintain serum triglycerides < 400 mg/dL
  • optimal timing & route of feeding in patients with acute pancreatitis remains controversial
• prognostic information provided by
  • Ranson criteria
  • modified Glasgow criteria
  • severity index for acute pancreatitis
  • bedside index for severity in acute pancreatitis
  • pancreatis necrosis most important prognostic factor
  • serial serum urea nitrogen provides the most reliable routine laboratory test to predict mortality
• prevention
  • a diet high in vegetables is associated with reduced risk of non-gallstone related acute pancreatitis
  • rectal indomethacin for individuals at high risk for post-ERCP pancreatitis
    • pancreatic duct stents for patients at high risk for post-ERCP pancreatitis receiving rectal indomethacin.

More general terms

• pancreatitis
• acute inflammation

More specific terms

• acute necrotizing pancreatitis
• gallstone pancreatitis

Additional terms

• bedside index for severity in acute pancreatitis (BISAP)
• causes of acute pancreatitis
• chronic pancreatitis
• modified Glasgow criteria
• Ranson criteria
• severity index for acute pancreatitis

Patient information

acute pancreatitis patient information