Acute Pancreatitis

Definition, Etiology, PathogenesisTop

Acute pancreatitis is an acute inflammatory condition associated with premature activation of pancreatic zymogens (primarily trypsin), a varying degree of damage to the adjacent tissues, and, in some cases, also to distant organs.

Causes: The most frequent causes include diseases of the gallbladder and alcohol use (these are responsible for ~80% of cases), idiopathic etiology (~10% of cases), iatrogenic factors (endoscopic retrograde cholangiopancreatography [ERCP], abdominal surgical procedures), hypertriglyceridemia (in particular chylomicronemia syndrome) >1000 mg/dL (11.3 mmol/L), hyperparathyroidism, drugs (including asparaginase, pentamidine, azathioprine, glucocorticoids, cytarabine), congenital malformations (pancreas divisum), abdominal trauma, postoperative complications; and very rarely, viral infection (coxsackievirus, mumps virus, cytomegalovirus, HIV), parasites (ascaris), genetic factors (eg, mutations of the SPINK1 gene, which encodes a trypsin inhibitor; cystic fibrosis), autoimmune diseases (systemic lupus erythematosus, Sjögren syndrome).

Acute pancreatitis is classified into 2 types:

1) Interstitial pancreatitis, which affects 80% to 90% of patients and is not associated with necrosis of the pancreas or the adjacent tissues; on imaging one may see diffuse or localized edema or enlargement, blurred margins of pancreas/surrounding tissues, and/or fluid collections.

2) Necrotizing pancreatitis, with necrosis of the pancreatic parenchyma and possibly adjacent tissues.

Clinical Features and Natural HistoryTop

1. Signs and symptoms: Abdominal pain (usually the cardinal symptom; the pain has a sudden onset, is very severe, and is located in the epigastrium or left upper abdominal quadrant; sometimes may be referred to the spine), nausea and vomiting that bring no relief of discomfort, fever (a frequent manifestation; the time of onset is important for determination of the cause and clinical importance of fever: onset in the first week suggests fever caused by systemic inflammatory response syndrome [SIRS], which resolves once the intensity of the inflammatory reaction has decreased; onset of fever in the second or third week is usually associated with infection of the necrotic tissues), epigastric pain, weak or absent peristalsis (paralytic ileus), increased abdominal wall muscle tone, palpable tender epigastric mass (observed in some patients with severe acute pancreatitis; this is caused by expanding necrosis and peripancreatic inflammatory infiltrates), altered mental status (a sign of developing shock, hypoxemia, and endotoxemia; disturbances of consciousness and restlessness can progress to pancreatic encephalopathy), tachycardia (common), hypotension (usually results from hypovolemia), sometimes shock (10% of cases), jaundice (in 20%-30% of patients, particularly with acute pancreatitis caused by biliary disease), rarely cutaneous manifestations (patients with severe acute pancreatitis and shock may develop facial erythema, cyanosis of the face and extremities, bruising around the umbilicus [Cullen sign] or in the lumbar area [Turner sign]), pleural effusion (in ~40% of patients; most frequently left sided).

2. Two overlapping phases of acute pancreatitis have been described: an early phase (characterized by systemic responses to the local pancreatic injury) and a late phase (with infection of necrotic tissues and septic complications). The early phase usually lasts 1 week, but sometimes may persist for 2 weeks. The onset of the second phase of acute pancreatitis, which lasts from a few weeks to a few months, confirms the diagnosis of a moderate to severe disease.

DiagnosisTop

Diagnostic Tests

1. Laboratory tests:

1) Abnormalities typical of acute pancreatitis: Elevated levels of pancreatic enzymes (usually >3 × upper limit of normal [ULN]):

a) Serum lipase: This has the highest sensitivity and specificity in diagnosing acute pancreatitis.

b) Serum and urine amylase: After 48 to 72 hours serum amylase levels often return to normal despite the ongoing disease; however, total urine amylase and serum pancreatic isoenzyme levels continue to be elevated.

2) Abnormalities related to the severity of acute pancreatitis or to its complications: Elevated white blood cell counts with a left shift in the differential count, elevated C-reactive protein (CRP) levels (this correlates with the severity of acute pancreatitis, particularly within the first 48 to 72 h), elevated serum procalcitonin levels (this correlates with the severity of acute pancreatitis as well as with the risk of organ failure and infected pancreatic necrosis), elevated blood urea/blood urea nitrogen (BUN) or serum creatinine levels (this may indicate inadequate fluid resuscitation in the initial stages of the disease or deterioration of renal function; it is an independent risk factor of death), biochemical markers of liver injury (hyperbilirubinemia, elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase; these suggest a biliary etiology of acute pancreatitis), elevated lactate dehydrogenase levels, hypoalbuminemia, relative erythrocytosis (due to dehydration [vomiting] and effusions [third space]) or anemia (due to bleeding), hypoxemia, hyperglycemia, hypertriglyceridemia, and hypocalcemia.

2. Imaging studies: Abdominal ultrasonography is the first-line study, but it often fails to visualize the pancreas (due to intestinal gas or obesity). In patients with acute pancreatitis ultrasonography may reveal pancreatic edema, an indistinct pancreatic outline, reduced and heterogeneous echogenicity of the pancreatic parenchyma; it may also visualize cholelithiasis and complications of acute pancreatitis (eg, fluid collections). Ultrasonography with IV contrast enhancement is used to visualize the pancreatic parenchyma. Contrast-enhanced computed tomography (CT) of the abdomen, the gold standard in diagnosing acute pancreatitis, is used to assess the presence and extent of pancreatic necrosis progressing A to E (or 0 to 4) from normal pancreas, through changes confined to the pancreas, inflammatory changes of the pancreas and peripancreatic tissues, to more advanced changes associated with single and then multiple and possibly infected fluid collections (CT severity index [CTSI] or Balthazar score). This study should not be routinely performed in patients in whom the diagnosis of acute pancreatitis is straightforward and the disease is mild and uncomplicated. CT should be performed in patients who do not improve within 48 to 72 hours (eg, those who have persistent pain, fever, and nausea, and in whom oral nutrition is not possible) to diagnose possible local complications, such as pancreatic necrosis. Abdominal CT performed between days 5 and 7 of the onset of the disease is optimal for the assessment of the extent of necrosis. CT should be performed immediately in every patient with suspected acute pancreatitis who is critically ill or requires surgery. Follow-up studies are performed in case of clinical deterioration, progressive organ failure, or signs and symptoms of sepsis. Chest radiographs may demonstrate bibasilar atelectasis, pleural effusion (particularly if left sided), or acute respiratory distress syndrome. Plain abdominal radiographs may reveal fluid levels or intestinal loop distension (symptoms of paralytic ileus: see Adynamic Ileus). ERCP with therapeutic sphincterotomy should be performed as an emergency procedure in selected patients with coexisting cholangitis or persistent cholestasisEvidence 1Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to heterogeneity of results. Tse F, Yuan Y. Early routine endoscopic retrograde cholangiopancreatography strategy versus early conservative management strategy in acute gallstone pancreatitis. Cochrane Database Syst Rev. 2012 May 16;5:CD009779. doi: 10.1002/14651858.CD009779.pub2. Review. PMID: 22592743. Petrov MS, van Santvoort HC, Besselink MG, van der Heijden GJ, van Erpecum KJ, Gooszen HG. Early endoscopic retrograde cholangiopancreatography versus conservative management in acute biliary pancreatitis without cholangitis: a meta-analysis of randomized trials. Ann Surg. 2008 Feb;247(2):250-7. doi: 10.1097/SLA.0b013e31815edddd. Review. PMID: 18216529. (see below). Magnetic resonance cholangiopancreatography (MRCP) is performed in the acute phase of the disease in patients with equivocal diagnosis; however, it is mainly used as part of the diagnostics of cholelithiasis and assessment of the pancreatic duct in patients with fluid collections or cysts and fistulae in advanced stages of the disease.

3. Endoscopic ultrasonography is useful in the identification of etiologic factors in patients with a history of acute pancreatitis or idiopathic recurrent acute pancreatitis if the previous diagnostic studies have not revealed the disease. The test enables identification of smaller structural abnormalities like gallstones sized <5 mm, tumors, or fluid collections.

Diagnostic Criteria

Diagnosis is confirmed in patients in whom 2 out of the following 3 criteria are fulfilled:

1) Typical clinical manifestations (epigastric pain of sudden onset, often referred to the back).

2) Levels of pancreatic enzymes elevated >3 × ULN.

3) Results of imaging studies (abdominal ultrasonography, contrast-enhanced CT, or magnetic resonance imaging [MRI]) typical of acute pancreatitis.

Assessment of Severity and Prognosis in Acute Pancreatitis

Numerous classifications and scoring systems are available to describe imaging morphology, clinical severity, or prognosis. Some examples include:

1) The revised Atlanta classification of general clinical severity (2012):

a) Mild acute pancreatitis: No organ failure, no local complications, and no systemic complications.

b) Moderate acute pancreatitis: Transient (<48 h) organ failure, local complications (acute peripancreatic fluid collection, pseudocyst, necrosis, acute necrotizing collection, walled-off pancreatic necrosis), and/or systemic complications (eg, exacerbation of ischemic heart disease or chronic lung disease) without persistent organ failure.

c) Severe acute pancreatitis: Persistent (>48 h) organ failure and usually ≥1 local complication. Definitions of multiple organ dysfunction (a modified Marshall score): Table 1. Patients who develop organ failure within the first 24 hours of hospitalization and in whom the failure cannot be classified as transient or persistent should be initially managed as patients with severe acute pancreatitis; reevaluate the severity of acute pancreatitis after 24 hours, 48 hours, and 7 days from admission.

2) Features observed on admission and 48 hours later that indicate the risk of development of severe acute pancreatitis and increased risk of mortality (according to the Rankin risk score on admission and after 48 h or Glasgow-Imrie score 48 h after admission):

a) Clinical risk factors: Age >55 years, obesity (body mass index >30 kg/m2), altered consciousness status, alcohol-related etiologies, presence of comorbidities, presence of ≥2 SIRS factors (see Sepsis and Septic Shock), hypoxia.

b) Abnormal laboratory test results: Elevated or rising BUN, creatinine, or both; elevated glucose; decreased calcium levels.

c) Abnormal results of imaging studies: Pleural effusion, pulmonary infiltrates, or multiple or extensive extrapancreatic fluid collections.

In the bedside index of severity in acute pancreatitis (BISAP), a score ≥3 within the first 24 hours indicates severe pancreatitis, with 5 carrying >20% probability of mortality. In that score one point is granted for each BUN result >8.9 mmol/L (25 mg/dL); altered consciousness status; presence of ≥2 SIRS criteria; age >60 years; and pleural effusion. The CTSI and Acute Physiology and Chronic Health Evaluation (APACHE) II score are also used to assess severity of the disease. Of note, the severity of elevation of serum and urine levels of pancreatic enzymes is not included in those indices.

Differential Diagnosis

Differential diagnosis should include gastrointestinal (GI) perforation (gastric or duodenal ulcer, intestinal perforation), acute appendicitis, acute intestinal ischemia, dissecting aortic aneurysm, ectopic pregnancy, and myocardial infarction (particularly posterior wall infarction).

TreatmentTop

Treatment of the acute phase of the disease includes fluid resuscitation, pain management, and nutrition therapy. Other interventions depend on the severity of the disease and its complications.

Medical Treatment

1. Initial management:

1) Traditionally the management of acute pancreatitis included initially a large volume of fluid (≥250 mL/h of balanced crystalloids), while adjusting the infusion rate to the patient’s volume status, response to fluid, cardiovascular function, and renal function (these could be assessed on the basis of the heart rate, arterial blood pressure, urine output [≥0.5 mL/h], and central venous pressure [in some patients]). The 2022 Waterfall study found that such a strategy of aggressive fluid resuscitation, compared with a less intense moderate resuscitation strategy, resulted in an increased incidence of fluid overload without improving the severity of pancreatitis. Those strategies used 10 mL/kg versus 20 mL/kg boluses for clinical hypovolemia and baseline infusion rates of 1.5 mL/kg/h versus 3 mL/kg/h. Since this study, the enthusiasm for large-volume management has decreased and less aggressive volume management may be preferred.Evidence 2Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to generalizability. de-Madaria E, Buxbaum JL, Maisonneuve P, et al; ERICA Consortium. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. N Engl J Med. 2022 Sep 15;387(11):989-1000. doi: 10.1056/NEJMoa2202884. PMID: 36103415. 

2) Immediately treat electrolyte disturbances, particularly hypokalemia.

3) Use blood transfusion as per guidelines in critically ill patients.

4) In patients with hyperglycemia >13.9 mmol/L (250 mg/dL), administer insulin.

2. Pain management: There is no difference in the complication risk between opioids and other analgesic options. Opioids (IV morphine or hydromorphone) may be an appropriate choice in the treatment of pain in acute pancreatitis.Evidence 3Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to indirectness to patient-important outcomes and imprecision. Basurto Ona X, Rigau Comas D, Urrútia G. Opioids for acute pancreatitis pain. Cochrane Database Syst Rev. 2013 Jul 26;7:CD009179. doi: 10.1002/14651858.CD009179.pub2. Review. PMID: 23888429.

3. Nutrition therapy: In mild acute pancreatitis oral feeding can be started immediately if there is no nausea and vomiting. Initiation of feeding with a low-fat solid diet appears as safe as a clear liquid diet.Evidence 4Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to the relative imprecision and heterogeneous populations. Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD002837. doi: 10.1002/14651858.CD002837.pub2. Review. PMID: 20091534. Eckerwall GE, Tingstedt BB, Bergenzaun PE, Andersson RG. Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery--a randomized clinical study. Clin Nutr. 2007 Dec;26(6):758-63. Epub 2007 Aug 24. PMID: 17719703. Yi F, Ge L, Zhao J, et al. Meta-analysis: total parenteral nutrition versus total enteral nutrition in predicted severe acute pancreatitis. Intern Med. 2012;51(6):523-30. Epub 2012 Mar 15. PMID: 22449657. Singh N, Sharma B, Sharma M, et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial. Pancreas. 2012 Jan;41(1):153-9. doi: 10.1097/MPA.0b013e318221c4a8. PMID: 21775915. Jacobson BC, Vander Vliet MB, Hughes MD, Maurer R, McManus K, Banks PA. A prospective, randomized trial of clear liquids versus low-fat solid diet as the initial meal in mild acute pancreatitis. Clin Gastroenterol Hepatol. 2007 Aug;5(8):946-51; quiz 886. Epub 2007 Jul 5. PMID: 17613280; PMCID: PMC2034288. In patients with severe acute pancreatitis, start enteral nutrition within the first 24 to 48 hours (if possible) and add parenteral nutrition if enteral nutrition is not tolerated.

1) Enteral nutrition is administered using a nasogastric or nasojejunal tube. The preferred enteral formula might be semielemental nutrition, which is low in fat and higher in predigested protein than regular feeding formulas. It should be started at a low rate (10-20 mL/h) and slowly increased until the desired caloric intake is reached.Evidence 5Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to methodologic limitations. Poropat G, Giljaca V, Hauser G, Stimac D. Enteral nutrition formulations for acute pancreatitis. Cochrane Database Syst Rev. 2015 Mar 23;(3):CD010605. doi: 10.1002/14651858.CD010605.pub2. PMID: 25803695. Al-Omran M, Albalawi ZH, Tashkandi MF, Al-Ansary LA. Enteral versus parenteral nutrition for acute pancreatitis. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD002837. doi: 10.1002/14651858.CD002837.pub2. Review. PMID: 20091534. Eckerwall GE, Tingstedt BB, Bergenzaun PE, Andersson RG. Immediate oral feeding in patients with mild acute pancreatitis is safe and may accelerate recovery--a randomized clinical study. Clin Nutr. 2007 Dec;26(6):758-63. Epub 2007 Aug 24. PMID: 17719703. Yi F, Ge L, Zhao J, et al. Meta-analysis: total parenteral nutrition versus total enteral nutrition in predicted severe acute pancreatitis. Intern Med. 2012;51(6):523-30. Epub 2012 Mar 15. PMID: 22449657. Singh N, Sharma B, Sharma M, et al. Evaluation of early enteral feeding through nasogastric and nasojejunal tube in severe acute pancreatitis: a noninferiority randomized controlled trial. Pancreas. 2012 Jan;41(1):153-9. doi: 10.1097/MPA.0b013e318221c4a8. PMID: 21775915. Jacobson BC, Vander Vliet MB, Hughes MD, Maurer R, McManus K, Banks PA. A prospective, randomized trial of clear liquids versus low-fat solid diet as the initial meal in mild acute pancreatitis. Clin Gastroenterol Hepatol. 2007 Aug;5(8):946-51; quiz 886. Epub 2007 Jul 5. PMID: 17613280; PMCID: PMC2034288. Complications are rare and minor (dislocation or obstruction of the tube, diarrhea, nausea, and flatulence caused by too rapid administration of the nutrition formulas).

2) Total parenteral nutrition (TPN) should be avoided in patients with mild and severe acute pancreatitis and used only if enteral nutrition is not possible. Monitor and treat metabolic disturbances (hypoglycemia and hyperglycemia, hypocalcemia, hypokalemia and hyperkalemia, hypophosphatemia, hypomagnesemia, and acid-base disturbances). Discontinue TPN promptly once enteral nutrition becomes feasible.

4. Antibiotic therapy: Do not use routine antibiotic prophylaxis in patients with severe acute pancreatitis or in patients with sterile pancreatic necrosis to prevent its infection.Evidence 6Strong recommendation (downsides clearly outweigh benefits; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to imprecision (lack of power). Villatoro E, Mulla M, Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev. 2010 May 12;(5):CD002941. doi: 10.1002/14651858.CD002941.pub3. Review. PMID: 20464721. Dellinger EP, Tellado JM, Soto NE, et al. Early antibiotic treatment for severe acute necrotizing pancreatitis: a randomized, double-blind, placebo-controlled study. Ann Surg. 2007 May;245(5):674-83. PMID: 17457158; PMCID: PMC1877078. Pederzoli P, Bassi C, Vesentini S, Campedelli A. A randomized multicenter clinical trial of antibiotic prophylaxis of septic complications in acute necrotizing pancreatitis with imipenem. Surg Gynecol Obstet. 1993 May;176(5):480-3. PMID: 8480272. Antibiotics are indicated in the treatment of infected pancreatic necrosis (see Complications, below) and extrapancreatic infections: cholangitis, catheter-related infections, bacteremia, urinary tract infections, pneumonia. Infected pancreatic necrosis should be suspected in the setting of positive blood cultures or evidence of gas within a pancreatic fluid collection on CT imaging. Antifungal therapy should not be routinely used in patients treated with antibiotics. Those decisions may be guided by fine-needle aspiration of fluid, especially if there is no adequate response to empiric antibiotics or when a fungal infection is suspected.Evidence 7Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Low Quality of Evidence (low confidence that we knowtrue effects of the intervention). Quality of Evidence lowered due to the lack of randomized controlled trials or meta-analyses. The recommendation is based on a consensus statement based on observational evidence and it has been adapted by most specialized centers. Freeman ML, Werner J, vanSantvoort HC, et al; International Multidisciplinary Panel of Speakers andModerators. Interventionsfor necrotizing pancreatitis: summary of a multidisciplinary consensusconference. Pancreas. 2012 Nov;41(8):1176-94. doi:10.1097/MPA.0b013e318269c660. PMID: 23086243.

Invasive Treatment

1. ERCP with sphincterotomy is indicated within 24 hours of admission in patients with coexisting acute cholangitis. It is not necessary in the majority of patients with biliary acute pancreatitis without laboratory or clinical features of persistent biliary obstruction. In patients without cholangitis and/or jaundice but with a well-grounded suspicion of biliary duct stones, endoscopic ultrasonography (EUS) or MRCP should be performed rather than a diagnostic ERCP.Evidence 8Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to heterogeneity of results. Tse F, Yuan Y. Early routine endoscopic retrograde cholangiopancreatography strategy versus early conservative management strategy in acute gallstone pancreatitis. Cochrane Database Syst Rev. 2012 May 16;5:CD009779. doi: 10.1002/14651858.CD009779.pub2. Review. PMID: 22592743. Petrov MS, van Santvoort HC, Besselink MG, van der Heijden GJ, van Erpecum KJ, Gooszen HG. Early endoscopic retrograde cholangiopancreatography versus conservative management in acute biliary pancreatitis without cholangitis: a meta-analysis of randomized trials. Ann Surg. 2008 Feb;247(2):250-7. doi: 10.1097/SLA.0b013e31815edddd. Review. PMID: 18216529.

2. Cholecystectomy: In patients with mild biliary acute pancreatitis, cholecystectomy should be performed before discharge unless it is contraindicated for other reasons. In patients with severe biliary acute pancreatitis, cholecystectomy is performed after the resolution of active inflammation and resorption or stabilization of fluid collections (usually after 6-8 wks).Evidence 8Weak recommendation (benefits likely outweigh downsides, but the balance is close or uncertain; an alternative course of action may be better for some patients). Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to methodologic limitations. Mueck KM, Wei S, Pedroza C, et al. Gallstone Pancreatitis: Admission Versus Normal Cholecystectomy-a Randomized Trial (Gallstone PANC Trial). Ann Surg. 2019 Sep;270(3):519-527. doi: 10.1097/SLA.0000000000003424. PMID: 31415304. Moody N, Adiamah A, Yanni F, Gomez D. Meta-analysis of randomized clinical trials of early versus delayed cholecystectomy for mild gallstone pancreatitis. Br J Surg. 2019 Oct;106(11):1442-1451. doi: 10.1002/bjs.11221. Epub 2019 Jul 3. PMID: 31268184. Gurusamy KS, Nagendran M, Davidson BR. Early versus delayed laparoscopic cholecystectomy for acute gallstone pancreatitis. Cochrane Database Syst Rev. 2013 Sep 2;9:CD010326. doi: 10.1002/14651858.CD010326.pub2. Review. PMID: 23996398.

3. Debridement of pancreatic necrosis: Infection of the necrosis is an indication for invasive procedures to evacuate the infected tissues. In stable patients with infected necrosis, surgical, endoscopic, or radiologic drainage procedures preferably should be delayed for >4 weeks to allow the development of a fibrous wall around the necrosis. Minimally invasive methods of necrosectomy are usually preferred to open necrosectomy.Evidence 9Strong recommendation (benefits clearly outweigh downsides; right action for all or almost all patients). Moderate Quality of Evidence (moderate confidence that we know true effects of intervention). Quality of Evidence lowered due to the paucity of randomized trials and the lack of meta-analysis. Freeman ML, Werner J, van Santvoort HC, et al; International Multidisciplinary Panel of Speakers and Moderators. Interventions for necrotizing pancreatitis: summary of a multidisciplinary consensus conference. Pancreas. 2012 Nov;41(8):1176-94. doi: 10.1097/MPA.0b013e318269c660. PMID: 23086243. Bakker OJ, van Santvoort HC, van Brunschot S, et al; Dutch Pancreatitis Study Group. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial. JAMA. 2012 Mar 14;307(10):1053-61. doi: 10.1001/jama.2012.276. PMID: 22416101. van Santvoort HC, Besselink MG, Bakker OJ, et al; Dutch Pancreatitis Study Group. A step-up approach or open necrosectomy for necrotizing pancreatitis. N Engl J Med. 2010 Apr 22;362(16):1491-502. doi: 10.1056/NEJMoa0908821. PMID: 20410514.

Follow-UpTop

In patients with severe acute pancreatitis, intensive care is required:

1) Monitor arterial blood pressures, pulse, and fluid balance hourly.

2) Monitor arterial blood gas and serum electrolyte levels frequently (a reasonable rate is every 4-12 h).

3) Perform physical examination at least every 12 hours.

4) Monitor pancreatic enzyme levels, the complete blood count, prothrombin time (PT), activated partial thromboplastin time (aPTT), biochemical kidney function tests, CRP, total protein and albumin levels, and, if necessary, also a 24-hour glucose profile on a daily basis.

5) Assess organ failure using the Marshall score on a daily basis over the first 7 days.

6) Periodically perform ultrasonography or CT.

ComplicationsTop

1. Acute peripancreatic fluid collection (APFC) develops early, usually in the first 24 to 48 hours of interstitial pancreatitis, and has no distinct wall visible on ultrasonography or CT. The contents are liquid. APFC results from rupture of the pancreatic ducts or from accumulation of inflammatory exudate. APFC is usually reabsorbed within 4 weeks, but in rare cases it may transform into a pseudocyst.

2. Pseudocysts develop from APFCs that have not been reabsorbed within 4 weeks. The wall of a pseudocyst is usually a capsule made of fibrous connective tissue lined with granulation tissue. Pseudocysts may also involve parts of the adjacent organs, such as the stomach, intestines, or pancreas. Similarly to APFC, the contents of pseudocysts are liquid.

3. Acute necrotic collection (ANC) develops in the early phase of necrotizing acute pancreatitis and may undergo complete reabsorption (if necrosis affects <30% of the pancreas) or gradual liquefaction with subsequent formation of a capsule. The contents of ANCs consist of varying amounts of solid debris (necrotic tissue), which differentiate ANC from APFC and pseudocysts. ANC may become infected. MRI, EUS, and abdominal ultrasonography are useful in differential diagnosis.

4. Walled-off necrosis (WON) is a late ANC that contains a variable amount of liquid and solid debris encapsulated in a thick wall, which reduces the probability of spontaneous reabsorption. WON usually develops ≥4 weeks from the onset of necrotizing acute pancreatitis. It may be asymptomatic or manifest with abdominal pain, duodenal obstruction, and/or biliary obstruction.

5. Infected necrosis of the pancreas and adjacent tissues usually develops during week 3 of the disease; mortality rates are as high as 50%. It should be suspected in patients with pancreatic or extrapancreatic necrosis who deteriorate or who do not improve within 7 to 10 days of hospital treatment. Diagnosis is based on positive blood cultures or evidence of gas in the necrotic tissue on a CT scan or alternatively with percutaneous FNA. An acceptable approach in patients with suspected pancreatic necrosis (after day 10-15) is IV empiric antimicrobial therapy with a carbapenem (doripenem, ertapenem, imipenem/cilastatin 1 g every 8 h, or meropenem 500 mg every 8 h) or a quinolone (ciprofloxacin 200 mg every 12 h, moxifloxacin or pefloxacin) in combination with metronidazole 500 mg every 8 hours. Invasive procedures are usually necessary (see Invasive Treatment, above); in selected, relatively stable patients, the invasive procedures may be delayed or spared, as long as strict monitoring can be ensured.

6. Fistulae: A late complication of necrotizing acute pancreatitis, which results from partial or total loss of continuity of the pancreatic ducts. Total loss of continuity with fluid leakage is known as disconnected pancreatic duct syndrome (DPDS). Leakage of fluids may lead to formation of acute or chronic fluid collections (pseudocysts) or fistulas (communication between 2 epithelized areas, most frequently with the duodenum or transverse colon but possibly also with pleural or peritoneal cavity). Symptoms may vary from none to abdominal manifestations including pain, nausea, vomiting, and/or distension, or even to dyspnea and cough with pleural fistulae. Diagnosis: MRCP (noninvasive) or ERCP (this offers a possibility of therapeutic stenting to improve healing). In patients with enteric fistulae, perform oral contrast–enhanced CT. Treatment: Most fistulae close spontaneously without the need of surgical intervention. Elements of supportive treatment may include enteral nutrition and endoscopic interventions (fluid collection drainage). The role of octreotide is not clear. Surgical intervention may be required.

7. Vascular complications:

1) Prehepatic portal hypertension caused by compression or occlusion of the splenic vein or the superior mesenteric vein.

2) Bleeding or pseudoaneurysm due to direct erosion of the pancreatic or peripancreatic arteries or veins (or both; most commonly the splenic, gastroduodenal, and pancreaticoduodenal vessels). Rupture of a pseudoaneurysm leads to a massive hemorrhage to the pseudocyst, peritoneal cavity, or into the GI tract. In patients with pseudoaneurysms communicating with the pancreatic duct, GI bleeding may occur via the ampulla of Vater.

3) Thrombosis of the splenic vein, splenic artery, or portal vein (see Portal Vein Thrombosis).

Diagnosis: CT, MRI, Doppler ultrasonography, selective splanchnic angiography (this allows for stopping the bleeding and occlusion of the pseudoaneurysm). Depending on the location, surgery may be required.

8. Organ complications: Early complications result from SIRS (see Sepsis and Septic Shock): shock, acute respiratory distress syndrome, acute kidney injury, disseminated intravascular coagulation, sepsis, and abdominal compartment syndrome.

TablesTop