> Table of Contents > Pancreatitis, Acute
Pancreatitis, Acute
Robert L. Frachtman, MD, FACG
Marni Martinez, APRN
image BASICS
DESCRIPTION
Acute inflammatory process of the pancreas with variable involvement of regional tissue or remote organ systems
  • Inflammatory episode with symptoms related to intrapancreatic activation of enzymes with pain, nausea and vomiting, and associated intestinal ileus
  • Varies widely in severity, complications, and prognosis, accounting for 280,000 hospital admissions per year in the United States
  • Complete structural and functional recovery if there is no necrosis or pancreatic ductal disruption.
EPIDEMIOLOGY
Incidence
  • 1 to 5/10,000
  • Predominant age: none
  • Predominant sex: male = female
Prevalence
Acute: 19/10,000
ETIOLOGY AND PATHOPHYSIOLOGY
  • Alcohol
  • Gallstones (including microlithiasis)
  • Trauma/surgery
  • Acute discontinuation of medications for diabetes or hyperlipidemia
  • Following endoscopic retrograde cholangiopancreatography (ERCP)
  • Medications (most common, not an exhaustive list)
    • ACE inhibitors
    • Angiotensin receptor blockers (ARBs)
    • Thiazide diuretics and furosemide
    • Antimetabolites (mercaptopurine and azathioprine) (1)
    • Corticosteroids
    • Glyburide
    • Exenatide (Byetta) (2)
    • Mesalamine
    • Pentamidine
    • Sulfamethoxazole/trimethoprim
    • Valproic acid
    • HMG-CoA reductase inhibitors, especially simvastatin (1)
    • Review all medications and continue only if the benefit outweighs risk, if medication is causally implicated.
  • Metabolic causes
    • Hypertriglyceridemia (>1,000 mg/dL)
    • Hypercalcemia
    • Acute renal failure
    • Diet with high glycemic load (3)[B]
    • Systemic lupus erythematosus/polyarteritis
    • Autoimmune pancreatitis, associated with elevated IgG4
    • Infections (list not exhaustive)
      • Mumps, coxsackie, cryptosporidiosis
  • Penetrating peptic ulcer (rare)
  • Cystic fibrosis and CFTR gene mutations
  • Tumors (e.g., pancreatic, ampullary) (4)
  • Pancreas divisum
  • Sphincter of Oddi dysfunction
  • Scorpion venom
  • Vascular disease
  • Acute fatty liver of pregnancy
  • Idiopathic/autoimmune
  • Pathophysiology—enzymatic “autodigestion” of the pancreas, interstitial edema with severe interstitial acute fluid accumulation (“3rd spacing”), hemorrhage, necrosis, release of vasoactive peptides (within 6 weeks), pseudocyst or acute necrotic collection (>6 weeks), pancreatic ductal disruption, injury to surrounding vascular structures like splenic vein (thrombosis) and splenic artery (pseudoaneurysm)
Genetics
Hereditary pancreatitis is rare. Autosomal dominant
GENERAL PREVENTION
  • Avoid excess alcohol consumption.
  • Tobacco cessation
  • Correct underlying metabolic processes (hypertriglyceridemia or hypercalcemia).
  • Discontinue offending medications.
  • Cholecystectomy (symptomatic cholelithiasis)
  • Diet with low glycemic load (3)[B]
COMMONLY ASSOCIATED CONDITIONS
  • Alcohol withdrawal, alcoholic hepatitis, diabetic ketoacidosis, and ascending cholangitis
  • Obesity increases severity, local complications, and mortality (5).
image DIAGNOSIS
Symptoms do not always correlate directly with objective findings (imaging, amylase/lipase).
PHYSICAL EXAM
  • Vital signs—assess hemodynamic stability; fever
  • Abdominal findings: epigastric tenderness, loss of bowel sounds
  • Other findings: jaundice, rales/percussive dullness
  • Rare (with hemorrhagic pancreatitis)
    • Flank discoloration (Grey-Turner sign) or umbilical discoloration (Cullen sign)
DIAGNOSTIC TESTS & INTERPRETATION
  • Interpret laboratory and radiographic findings in the context of the clinical history, as false-positive and false-negative findings are common.
  • American College of Gastroenterology require at least 2 of the 3 following elements to make a diagnosis of acute pancreatitis: characteristic abdominal pain, specific radiographic findings, and lipase level 3 times the ULN.
  • Elevated serum amylase >3 times upper limit of normal (ULN) (severity is not related to degree of elevation)
  • Elevated serum lipase >3 times ULN (may stay elevated longer than amylase in mild cases)
  • Elevated total bilirubin. If >3 mg/dL, consider common bile duct obstruction.
  • Transaminases rise quickly with acute bile duct obstruction. They also fall rapidly as alkaline phosphatase rises; a 3-fold elevation in the alanine aminotransferase (ALT) in the setting of acute pancreatitis has a 95% positive predictive value for gallstone pancreatitis. Triglyceride levels >1,000 mg/dL suggest hypertriglyceridemia as the cause.
  • Glucose is increased in severe disease.
  • Calcium is decreased in severe disease.
  • WBC elevation to 10,000 to 25,000/&mgr;L possible and not indicative of active infection
  • Rising hemoglobin is a poor prognostic sign (severe 3rd spacing-hemoconcentration). Rising blood urea nitrogen (BUN) and creatinine imply volume depletion or acute renal failure.
DIFFERENTIAL DIAGNOSIS
  • Penetrating peptic ulcer
  • Acute cholecystitis or cholangitis
  • Macroamylasemia, macrolipasemia
  • Mesenteric vascular occlusion and/or infarction
  • Perforation of a viscus
  • Intestinal obstruction
  • Aortic aneurysm (dissecting or rupturing)
  • Inferior wall myocardial infarction
  • Lymphoma
Initial Tests (lab, imaging)
  • Use follow-up labs to assess renal function, hydration, sepsis, biliary obstruction, and tissue oxygenation status.
  • Plain film of abdomen helps rule out mechanical small bowel obstruction. Ileus is common.
  • Chest x-ray (CXR) to evaluate for early acute respiratory distress syndrome (ARDS) and pleural effusion; can also rule out free subdiaphragmatic air.
  • Ultrasound to rule out cholelithiasis; choledocholithiasis can occasionally be seen.
  • CT scan
    • Confirms the diagnosis, assesses severity, establishes a baseline, and rules out other possibilities. CT does not rule out noncalcified cholelithiasis.
    • IV contrast is not essential on the initial CT scan and should be avoided in volume-depleted patients.
    • If not contraindicated, a CT scan with IV contrast at day 3 can assess the degree of necrosis when necrotizing pancreatitis is suspected because of O2 saturation <90%, systolic BP <90 mm Hg, and so forth.
  • MRCP helps assess for choledocholithiasis, pancreas divisum, a dilated pancreatic duct, and chronic ductal changes.
  • Esophagogastroduodenoscopy (EGD) may be necessary to rule out a penetrating duodenal ulcer or an obstructing ampullary neoplasm if suggested by laboratory or imaging studies.
  • ERCP may be necessary to decompress common bile duct due to an impacted stone.
  • Endoscopic ultrasonography (EUS) is useful when a patient presents with “idiopathic pancreatitis”(4)[B].
  • FNA may be added to EUS if autoimmune pancreatitis is suspected (6)[C].
Follow-Up Tests & Special Considerations
If renal function is stable, a contrast-enhanced CT scan at day 3 to assess for necrosis. Later in the course, if there is a spike in the temperature, CT-guided aspiration can help assess secondary infection.
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image TREATMENT
MEDICATION
First Line
  • Analgesia: no consensus; guidelines vary widely on types and dosing for analgesia (7).
    • Hydromorphone (Dilaudid) 0.5 to 1 mg IV q1-2h PRN
    • AVOID Demerol due to the potential of accumulation of a toxic metabolite.
  • Antibiotics
    • The use of prophylactic antibiotics is no longer recommended, even with necrotizing pancreatitis, in the absence of infection.
    • In patients with ascending cholangitis or necrotizing pancreatitis, &bgr;-lactam/&bgr;-lactamase inhibitor (e.g., piperacillin/tazobactam 4.5 g IV q8h) can be considered for initial treatment, before cultures (especially of aspirated collections) return, if there is a strong suspicion of active infection.
    • Levofloxacin 500 mg QD IV if cholangitis and there is an allergy to penicillin
    • Be vigilant for monilial superinfections when giving prophylactic antibiotics.
GENERAL MEASURES
Most cases of acute pancreatitis require hospitalization; ICU if multiorgan dysfunction or hypotension/respiratory failure. 15-20% of cases of acute pancreatitis progress from mild to severe (including persistent organ failure).
  • Fluid resuscitation
    • Significant volume deficit due to 3rd spacing
    • Infuse bolus of 1,000 to 2,000 mL (lactated Ringers may be better than normal saline, unless hypercalcemic) (8)[C], followed by 250 to 300 mL/hr, adjusted on the basis of age, weight, hemodynamic response, and comorbid conditions.
    • Target urine output should be 0.5 to 1 mL/kg/hr. Lower infusion rate when this goal is achieved or once BUN decreases; 4 L should be the maximum fluid on day 1.
  • Eliminate unnecessary medications, especially those potentially causing pancreatitis.
  • Nasogastric (NG) tube for intractable emesis
  • Follow renal function, volume status, calcium, and oxygenation. Organ failure is more important prognostic indicator than pancreatic necrosis.
  • Intermittent pneumatic compression device
  • Begin oral alimentation after pain, tenderness, and ileus have resolved; small amounts of highcarbohydrate, low-fat, and low-protein foods; advance as tolerated; NPO or NG tube if vomiting persists.
  • Enteral nutrition at level of ligament of Treitz if oral feeding not possible within 5 to 7 days (preferable to total parenteral nutrition [TPN] due to decreased infection rate and decreased mortality). Discontinue with increases in pain, amylase/lipase levels, or fluid retention.
  • TPN (without lipids if triglycerides are elevated) if oral or nasoenteric feedings are not tolerated (9).
ISSUES FOR REFERRAL
Refer to a tertiary center if pancreatitis is severe or actively evolving and when advanced imaging or endoscopic therapy is being considered.
SURGERY/OTHER PROCEDURES
  • Consider cholecystectomy before discharge in patients with cholelithiasis and nonnecrotizing pancreatitis to reduce risk of recurrent acute gallstone pancreatitis.
  • Necrosectomy should be performed nonsurgically for either infected or noninfected necrosis. Walled off necrosis should be observed for 4 weeks (treated with antibiotics if infected), followed by percutaneous or dual-modality drainage if available (10,11)[B].
  • ERCP early if evidence of acute cholangitis or at 72 hours if evidence of ongoing biliary obstruction. ERCP with pancreatic ductal stent placement, if ductal disruption persists longer than 1 to 2 weeks.
  • Resection or embolization for bleeding pseudoaneurysms
  • Plasma exchange with insulin if necrotizing pancreatitis secondary to hypertriglyceridemia
INPATIENT CONSIDERATIONS
Discharge Criteria
  • Pain controlled
  • Tolerating oral diet
  • Alcohol rehabilitation and tobacco cessation
  • Low-grade fever and mild leukocytosis do not necessarily indicate infection and may take weeks to resolve. Infections may occur even after 10 days (33% of patients with necrotizing pancreatitis) due to secondary infection of necrotic material, requiring surgical débridement.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Follow-up imaging studies in several weeks, if the original CT scan showed a fluid collection or necrosis or if the amylase/lipase continues to be elevated. Follow-up findings may include:
    • Pseudocyst (occurs in 10%) or abscess (sudden onset of fever): Conservative management is an option for asymptomatic pseudocysts up to 6 cm in diameter.
    • Splenic vein thrombosis (gastric variceal hemorrhage rarely occurs)
    • Pseudoaneurysm (splenic, gastroduodenal, intrapancreatic) hemorrhage can be life-threatening.
  • Mild exocrine and endocrine dysfunction is usually subclinical. Patients with necrotizing pancreatitis, steatorrhea, or ductal obstruction should receive enzyme supplementation.
DIET
Continue to advance diet as tolerated. Dietary modification to reduce dietary fats, alcohol, and added sugars.
PROGNOSIS
85-90% of cases of acute pancreatitis resolve spontaneously; 3-5% mortality (17% in necrotizing pancreatitis)
REFERENCES
1. Nitsche CJ, Jamieson N, Lerch MM, et al. Drug induced pancreatitis. Best Pract Res Clin Gastroenterol. 2010;24(2):143-155.
2. Wang SQ, Li SJ, Feng QX, et al. Overweight is an additional prognostic factor in acute pancreatitis: a meta-analysis. Pancreatology. 2011;11(2): 92-98.
3. Oskarsson V, Sadr-Azodi O, Orsini N, et al. High dietary glycemic load increases the risk of nongallstone-related acute pancreatitis: a prospective cohort study. Clin Gastroenterol Hepatol. 2014;12(4):676-682.
4. Munigala S, Kanwal F, Xian H, et al. Increased risk of pancreatic adenocarcinoma after acute pancreatitis. Clin Gastroenterol Hepatol. 2014;12(7):1143-1150.e1.
5. Wu BU, Conwell DL. Acute pancreatitis part I: approach to early management. Clin Gastroenterol Hepatol. 2010;8(5):410-416.
6. Iwashita T, Yasuda I, Doi S, et al. Use of samples from endoscopic ultrasound-guided 19-gauge fine-needle aspiration in diagnosis of autoimmune pancreatitis. Clin Gastroenterol Hepatol. 2012;10(3):316-322.
7. Oláh A, Romics L Jr. Evidence-based use of enteral nutrition in acute pancreatitis. Langenbecks Arch Surg. 2010;395(4):309-316.
8. Hoque R, Farooq A, Ghani A, et al. Lactate reduces liver and pancreatic injury in toll-like receptor- and inflammasome-mediated inflammation via GPR81-mediated suppression of innate immunity. Gastroenterology. 2014;146(7): 1763-1774.
9. Gravante G, Garcea G, Ong SL, et al. Prediction of mortality in acute pancreatitis: a systematic review of the published evidence. Pancreatology. 2009;9(5):601-614.
10. Trikudanathan G, Attam R, Arain MA, et al. Endoscopic interventions for necrotizing pancreatitis. Am J Gastroenterol. 2014;109(7):969-981.
11. Ross AS, Irani S, Gan SI, et al. Dual-modality drainage of infected and symptomatic walled-off pancreatic necrosis: long-term clinical outcomes. Gastrointest Endosc. 2014;79(6):929-935.
Additional Reading
&NA;
  • Fisher JM, Gardner TB. The “golden hours” of management in acute pancreatitis. Am J Gastroenterol. 2012;107(8):1146-1150.
  • Lu X, Aoun E. Complications of acute pancreatitis. Pract Gastroenterol. 2012;36:11-22.
  • Wu BU, Banks PA. Clinical management of patients with acute pancreatitis. Gastroenterology. 2013;144(6):1272-1281.
Codes
&NA;
ICD10
  • K85.9 Acute pancreatitis, unspecified
  • K85.8 Other acute pancreatitis
  • K85.2 Alcohol induced acute pancreatitis
Clinical Pearls
&NA;
  • BISAP score is easier to apply than Ranson criteria and just as accurate in predicting mortality in acute pancreatitis.
  • Review all medications upon admission and discontinue any that are implicated as causing pancreatitis.
  • Patients with mild pancreatitis can progress to severe pancreatitis over the initial 48 hours, often due to inadequate fluid replacement.
  • Referral to tertiary center is needed if acute pancreatitis is severe or evolving/worsening.