Acute Pancreatitis – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

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 ileusVaries widely in severity (including death), complications, and prognosisComplete structural and functional recovery, provided no necrosis or pancreatic ductal disruption

Epidemiology

Incidence

1–5/10,000Predominant age: nonePredominant sex: Male = Female

Prevalence

Acute: 19/10,000

Risk Factors

See Etiology.

Genetics

Hereditary pancreatitis is a rare condition with an autosomally dominant inheritance pattern.

General Prevention

Avoidance of alcohol excess, especially over a prolonged periodAvoidance of cigarette smokingCorrection of underlying causes (hypertriglyceridemia or hypercalcemia)Discontinuation of medications associated with pancreatitis as soon as it is diagnosedCholecystectomy if symptomatic cholelithiasis

Pathophysiology

Autodigestion of the pancreas, interstitial edema with severe third spacing, hemorrhage, necrosis, release of vasoactive peptides, acute fluid collection (within 6 weeks), pseudocyst or postnecrotic collection (greater than 6 weeks), pancreatic ductal disruption, injury to surrounding vascular structures such as the splenic vein (thrombosis) and splenic artery (pseudoaneurysm)

Etiology

AlcoholGallstones (including microlithiasis)Trauma/surgeryAcute discontinuation of medications for diabetes or hyperlipidemiaFollowing endoscopic retrograde cholangiopancreatography (ERCP)Medications (most common, but not exhaustive list): ACE inhibitorsARBs (angiotensin receptor blockers)Thiazide diuretics and furosemideAntimetabolites (Purinethol and azothioprine)CorticosteroidsExenatide (Byetta) (1)[A]PentamidineStatinsPancreatitis may occur only after several months’ administration of some of the implicated medications.When a patient presents with pancreatitis, all medications should be reviewed in the PDR and accessible literature and should be continued only if the benefit justifies the risk of continuing a potential cause of pancreatitis, especially if no other causes are identified.Metabolic causes: HypertriglyceridemiaHypercalcemiaAcute renal failureHereditary causes (uncommon)Systemic lupus erythematosus/polyarteritisInfections (list not exhaustive): Mumps, Coxsackie, CryptosporidiosisPenetrating peptic ulcer (rare)Cystic fibrosis and CFTR (cystic fibrosis transmembrane conductance regulator) gene mutationsTumors (e.g., ampullary)Pancreas divisumSphincter of Oddi dysfunctionScorpion venomVascular diseaseAcute fatty liver of pregnancyIdiopathic

Commonly Associated Conditions

Consider coexistent alcohol withdrawal, alcoholic hepatitis, and ascending cholangitis.

Diagnosis

Symptoms and objective evidence (imaging, amylase/lipase) do not always correlate.

History

Fairly rapid onset of epigastric pain, which may radiate posteriorly, often with emesisAlcohol useHistory of gallstonesFamily history of gallstonesMedication useAbdominal traumaRecent significant weight loss (via causing cholelithiasis)

Physical Exam

Abdominal findings: Epigastric tenderness, loss of bowel soundsOther findings: Fever, tachycardia, hypotension/shock, jaundice, rales/percussive dullnessRare (with hemorrhagic pancreatitis) Flank discoloration (Grey–Turner sign) or umbilical discoloration (Cullen sign)

Diagnostic Tests & Interpretation

The laboratory and radiographic assessment of both acute and chronic pancreatitis must be used together, as there can be many false positives and negatives.

Lab

Elevated serum amylase >3× upper limit of normal (severity is not related to degree of elevation)Elevated serum lipase >3× upper limit of normal (may stay elevated longer than amylase in mild cases)Elevated total bilirubin to 3 mg/dL is not uncommon with pancreatitis, per se, but more elevated levels create consideration of common bile duct obstruction.Transaminases can quickly rise to near 1000 u/l with acute bile duct obstruction, but should rapidly fall as the alkaline phosphatase rises; a 3-fold elevation in the ALT in the setting of acute pancreatitis has a 95% positive predictive value for gallstone pancreatitis.Triglyceride levels >1000 mg/dL suggest hypertriglyceridemia as the cause.Glucose is increased in severe disease.Calcium is decreased in severe disease.WBC’s can be 10,000–25,000/µL without active infection.Rising hemoglobin is a poor prognostic sign (severe third spacing). Rising BUN and creatinine imply volume depletion or acute renal failure.Disorders that may alter results for amylase or lipase: Biliary tract disease, penetrating peptic ulcer, intestinal obstruction, intestinal ischemia/infarction, ruptured ectopic pregnancy, renal insufficiency, burns, macroamylasemia, or macrolipasemia

Initial lab tests

Admit labs should be supplemented by early and frequent follow-up labs to assess renal function, hydration, sepsis, biliary obstruction, and O2 saturation.

Imaging

Plain film of abdomen is useful to rule out mechanical small bowel obstruction, but ileus secondary to pancreatitis is common.CXR is useful to evaluate for early ARDS and pleural effusion; if upright, can rule out free subdiaphragmatic air.Ultrasound is useful to rule out cholelithiasis; choledocholithiasis can occasionally be seen.CT scan: Will confirm the diagnosis, assess the severity, establish a baseline, and to rule out other possibilitiesIntravenous contrast is not essential on the initial CT scan regarding evaluation for necrosis and should be avoided in volume-depleted patients.A negative CT scan will not rule out noncalcified cholelithiasis.If not contraindicated, a CT scan with intravenous 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, etc.MRCP is useful (if it can be performed) to assess the likelihood of choledocholithiasis; as a bonus, one may find pancreas divisum, a dilated pancreatic duct, or chronic ductal changes.ERCP may be necessary for emergency common bile duct decompression due to an impacted stone.Endoscopic ultrasonography (EUS) may be useful when a patient with “idiopathic pancreatitis” has a second episode.

Initial approach

The ultrasound, followed quickly by the CT scan, has largely replaced the plain film of the abdomen.

Follow-Up & Special Considerations

If renal function is stable, a contrast-enhanced CT scan is very useful at day 3 to assess for necrosis, a major prognostic indicator. Later in the course, if a cavity develops and there is a sudden worsening in the temperature curve, material can be aspirated via CT scan to assess for secondary infection.

Differential Diagnosis

Penetrating peptic ulcerAcute cholecystitisCholedocholithiasisMacroamylasemia, macrolipasemiaMesenteric vascular occlusion and/or infarctionPerforation of a viscusIntestinal obstructionAortic aneurysm (dissecting or rupturing)Inferior wall myocardial infarctionLymphoma

Treatment

Medication

Analgesia: Hydromorphone (Dilaudid) .5–1 mg IV every 1–2 hours p.r.n. (morphine sulfate can increase Sphincter of Oddi pressure, worsening the pancreatitis and increasing ductal pressure)Demerol should be avoided due to the potential of accumulation of a toxic metabolite.Antibiotics: Carbapenems can be considered for prophylaxis in necrotizing/severe pancreatitis if >30% necrosis on the CT scan (the usage of prophylactic antibiotics remain controversial, however, and seems to be losing favor)Beta lactam blockers with semisynthetic penicillin (e.g., Zosyn) or fluoroquinolones if cholangitisBe vigilant for monilial superinfections when giving prophylactic antibiotics.

Additional Treatment

General Measures

Confirm diagnosis and rule out other possibilities, if needed (see above).Unless extremely mild, most cases require hospitalization.Fluid resuscitation: If moderate or severe pancreatitis, there could easily be a 3-liter deficit due to third spacing.Infusion rates of 500 ml/hour for the first several hours, followed by 200–300 ml per hour for 48 hours, would not be unreasonable in those circumstances.Urine output goal should be 0.5–1 mL/kg per hour.Eliminate all unnecessary medications, especially those that could potentially cause pancreatitis.Analgesia (see above)NG tube is needed only if there is intractable emesis.Follow status regarding renal function, volume, calcium, oxygenation.Imaging studies as needed (e.g., contrasted CT scan in 48–72 hours, if no contraindications, to evaluate for necrotizing pancreatitis, which increases the incidence of fluid collections)Intermittent pneumatic compression deviceEnteral nutrition at level of Ligament of Treitz if oral feeding will not be possible within 5–7 days (preferable to TPN due to decreased infection rate)TPN (without lipids if triglycerides are elevated) if oral or nasoenteric feedings are not tolerated

Issues for Referral

Refer to a tertiary center if pancreatitis is either already severe or actively evolving and when advanced imaging or endoscopic therapy is being considered.

Surgery/Other Procedures

Necrosectomy for infected necrosisERCP early if evidence of acute cholangitis or at 72 hours if evidence of ongoing biliary obstructionResection or embolization for bleeding pseudoaneurysmsPlasma exchange if necrotizing pancreatitis secondary to hypertriglyceridemia

In-Patient Considerations

Discharge Criteria

Pain controlDiet toleranceAlcohol rehab and smoking cessation, if neededLow-grade fever and mild leukocytosis do not necessarily indicate infection and may take weeks to resolve.

Ongoing Care

Follow-Up Recommendations

Follow up imaging studies may be required in several weeks, especially if the original CT scan showed a fluid collection or necrosis or if the amylase or lipase continue to be elevated. Pseudocyst or abscess (sudden onset of fever),Splenic vein thrombosis (gastric variceal hemorrhage can occur rarely)Pseudoaneurysm (splenic, gastroduodenal, intrapancreatic) hemorrhages (life threatening)Mild exocrine and endocrine dysfunction occur, but are usually subclinical.

Diet

Begin diet after pain, tenderness, and ileus have resolved; small amounts of high-carbohydrate, low-fat, and low-protein foods; advance as tolerated; NPO or nasogastric tube if patient is vomitingTotal parenteral nutrition (TPN) if oral is not tolerated (no lipids if triglycerides are increased) (2)[A]Enteral nutrition at level of Ligament of Treitz is preferable to TPN if tolerated (less infection, decreased organ failure).

Prognosis

85–90% resolve spontaneously; 3–5% mortality (17% in necrotizing pancreatitis). APACHE II scoring is most accurate but difficult to apply (3)[A]; Ranson criteria (see below) have a sensitivity of ~40%.

On admission: Age >55 years, WBCs >16,000/mm, blood glucose >200 mg/dL (11.1 mmol/L), serum lactate dehydrogenase (LDH) >350 IU/L, AST >250 IU/L.Within 48 hours: Hematocrit decreases >10%, serum calcium <8 mg/dL, blood urea nitrogen (BUN) increase >8 mg/dL, arterial PO2 <60 mmHg, base deficit >4 mEq/L, fluid retention >6 LRanson scoring: Ranson score of 0–2: Minimal mortalityRanson score of 3–5: 10–20% mortalityRanson score of >5: >50% mortality

References

1. Anderson SL, Trujillo JM et al. Association of pancreatitis with glucagon-like peptide-1 agonist use. Ann Pharmacother. 2010;44:904–9.

2. Oláh A, Romics L et al. Evidence-based use of enteral nutrition in acute pancreatitis. Langenbecks Arch Surg. 2010;395:309–16.

3. Gravante G, Garcea G, Ong SL, et al. Prediction of mortality in acute pancreatitis: a systematic review of the published evidence. Pancreatology. 2009;9:601–14.

Additional Reading

Wu BU, Conwell DL et al. Acute pancreatitis part I: approach to early management. Clin Gastroenterol Hepatol. 2010;8.

Wu BU, Conwell DL et al. Acute pancreatitis part II: approach to follow-up. Clin Gastroenterol Hepatol. 2010;8:417–22.

See Also (Topic, Algorithm, Electronic Media Element)

Substance Use Disorders; Choledocholithiasis; Peptic Ulcer Disease; Systemic Lupus Erythematosus (SLE)

Codes

ICD9

577.0 Acute pancreatitis

Snomed

197456007 acute pancreatitis (disorder)

Clinical Pearls

Review all medications upon admission and discontinue any that have been implicated as causing pancreatitis, especially ACE inhibitors (in this author’s experience).Fluid resuscitation is critical early since inadequate resuscitation has been implicated in converting mild pancreatitis into necrotizing pancreatitis.Referral to tertiary center is needed if acute pancreatitis is severe or evolving/worsening.Outpatient follow-up, particularly re-imaging, is very important.