BASICSRobert L. Frachtman, MD, FACG • Marni L. Martinez, APRN
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
• Acute pancreatitis is the most common gastrointestinal diagnosis for inpatient hospitalization.
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)
– Corticosteroids; glyburide; exenatide (Byetta)
– Mesalamine; pentamidine
– Sulfamethoxazole/trimethoprim
– Valproic acid
– HMG-CoA reductase inhibitors, especially simvastatin
– Review all medications and continue only if the benefit outweighs risk.
• Metabolic causes
– Hypertriglyceridemia (>1,000 mg/dL); hypercalcemia; acute renal failure
– Diet with high glycemic load
– Systemic lupus erythematosus/polyarteritis
– Autoimmune pancreatitis, with elevated IgG4
– Infections
Mumps, coxsackie, cryptosporidiosis
• Penetrating peptic ulcer (rare)
• Cystic fibrosis and CFTR gene mutations
• Tumors (e.g., pancreatic, ampullary)
• 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-splenic vein (thrombosis) and splenic artery (pseudoaneurysm)
• The severity of the first episode of acute pancreatitis, alcohol abuse, and smoking all increase the risk of acute recurrent pancreatitis, which, in turn, increases the risk of progression to chronic pancreatitis.
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
COMMONLY ASSOCIATED CONDITIONS
• Alcohol withdrawal, alcoholic hepatitis, diabetic ketoacidosis, and ascending cholangitis
• Morbid obesity, a proinflammatory state, increases severity and adverse outcomes (organ failure, mortality).
DIAGNOSIS
Symptoms do not always correlate with objective findings.
HISTORY
• Acute onset of “boring” epigastric pain, which may radiate posteriorly toward the back
• Nausea/vomiting
• Alcohol use
• Personal or family history of gallstones
• Medication use
• Abdominal trauma
• Recent significant rapid weight loss
PHYSICAL EXAM
• Vital signs—assess hemodynamic stability; fever
• Abdominal findings: epigastric tenderness, loss of bowel sounds, peritoneal signs
• 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.
• Bedside Index in Severity in Acute Pancreatitis (BISAP) score
• Patients receive 1 point for each condition in the first 24 hours: BUN > 25 mg/dL, impaired mental status, systemic inflammatory response syndrome (SIRS)—a score of 0 predicts mortality of <1%, and a score of 5 correlates with a mortality rate of 22%.
• Ranson criteria is an older model of predicting severity of pancreatitis. It includes 11 criteria, 5 of which are measured at admission and 6 are measured in the following 48 hours. A score of 3 or less represents mild pancreatitis, and as the score increases, the mortality rises sharply.
• American College of Gastroenterology requires at least two of the three following elements to make a diagnosis of acute pancreatitis: characteristic abdominal pain, specific radiographic findings, and lipase level 3 times the upper limits of normal (ULN).
• Elevated serum amylase >3× ULN (Severity is not related to degree of elevation.)
• Elevated serum lipase >3× 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/μL possible and not indicative of active infection
• Elevated baseline hematocrit >44 or rising hematocrit are poor prognostic signs (severe 3rd spacing with associated hemoconcentration) (1)[A].
• Rising BUN and creatinine imply volume depletion or acute renal failure (1)[A].
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.
• 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 subdiaphragmatic air (perforated viscus)
• Ultrasound to look for gallbladder/biliary stones
• CT scan
– Confirms the diagnosis, assesses severity, establishes a baseline, and rules out most other pathologies (excluding noncalcified cholelithiasis)
– IV contrast is not essential for the initial CT scan; avoid contrast in volume-depleted patients.
– If not contraindicated, a CT scan with IV contrast on day 3 can assess the degree of necrosis if necrotizing pancreatitis is suspected.
• Magnetic resonance cholangiopancreatography (MRCP) helps assess choledocholithiasis, pancreas divisum, dilated pancreatic duct, and ductal changes.
• Esophagogastroduodenoscopy (EGD) may be necessary to rule out a penetrating duodenal ulcer or an obstructing ampullary neoplasm.
• ERCP may be necessary to decompress common bile duct due to an impacted stone.
• Endoscopic ultrasonography (EUS) is useful if patients present with “idiopathic pancreatitis” (2)[B].
• FNA may be added to EUS if autoimmune pancreatitis is suspected (3)[B].
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 guidance assists aspiration and drainage of abscess.
TREATMENT
MEDICATION
First Line
• Analgesia: no consensus; guidelines vary widely on types and dosing for analgesia.
– 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 clear absence of infection.
– In patients with ascending cholangitis or necrotizing pancreatitis, β-lactam/β-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 fungal 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), 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 high-carbohydrate, 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 (4)[A]
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 (5)[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
ADMISSION, INPATIENT, AND NURSING 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.
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 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, however, should receive enzyme supplementation.
• After the first episode of acute pancreatitis, the risk of lifetime diabetes doubles.
• After the first episode of acute pancreatitis, the risk of developing acute recurrent pancreatitis is ~17%. The risk for developing chronic pancreatitis is ~8%.
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. Koutroumpakis E, Wu BU, Bakker OJ, et al. Admission hematocrit and rise in blood urea nitrogen at 24 h outperform other laboratory markers in predicting persistent organ failure and pancreatic necrosis in acute pancreatitis: a post hoc analysis of three large prospective databases. Am J Gastroenterol. 2015;110(12):1707–1716.
2. Munigala S, Kanwal F, Xian H, et al. Increased risk of pancreatic adenocarcinoma after acute pancreatitis. Clin Gastroenterol Hepatol. 2014;12(7):1143.e1–1150.e1.
3. 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.
4. 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.
5. Trikudanathan G, Attam R, Arain MA, et al. Endoscopic interventions for necrotizing pancreatitis. Am J Gastroenterol. 2014;109(7):969–981.
ADDITIONAL READING
• Ahmed Ali U, Issa Y, Hagenaars JC, et al. Risk of recurrent pancreatitis and progression to chronic pancreatitis after a first episode of acute pancreatitis. Clin Gastroenterol Hepatol. 2016;14(5):738–746.
• Lu X, Aoun E. Complications of acute pancreatitis. Pract Gastroenterol. 2012;36:11–22.
• Nitsche CJ, Jamieson N, Lerch MM, et al. Drug induced pancreatitis. Best Pract Res Clin Gastroenterol. 2010;24(2):143–155.
• Oláh A, Romics L Jr. Evidence-based use of enteral nutrition in acute pancreatitis. Langenbecks Arch Surg. 2010;395(4):309–316.
• 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.
• Wu BU, Banks PA. Clinical management of patients with acute pancreatitis. Gastroenterology. 2013;144(6):1272–1281.
CODES
ICD10
• K85.9 Acute pancreatitis, unspecified
• K85.8 Other acute pancreatitis
• K85.2 Alcohol induced acute pancreatitis
CLINICAL PEARLS
• Pancreatitis remains a common indication for hospitalization. Alcohol misuse and gallstones are the leading causes for pancreatitis
• The BISAP score is easier to apply than Ranson criteria and is just as accurate for predicting mortality in patients with acute pancreatitis.
• Review all medications and discontinue any that may cause (or contribute to) 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.