Epidemiology and General Information

• Pancreatitis is responsible for 30,000 emergency room visits in the U.S annually and is the most common GI cause of hospitalizations in the U.S
• Inflammation of the pancreas leads to hypersecretion and/or backflow of digestive enzymes into the pancreatic tissue, leading to autodigestion and capillary leak leading to local and systemic edema and third-spacing, and in severe cases a shock-like state
• Acute pancreatitis is caused by an acute trigger leading to inflammation and is reversible
• 20% of patients will develop moderately severe or severe pancreatitis which is characterized by organ failure and systemic complications
• Mortality is low in patients without evidence of organ failure, but as high as 30-50% in those with severe pancreatitis due to multiorgan dysfunction and risk of sepsis from infected pancreatic necrosis
• Chronic pancreatitis will eventually lead to irreversible damage to pancreatic functioning - it is mostly associated with chronic alcohol use. 
• Chronic pancreatitis does not present with pancreatic dysfunction until a vast majority of the pancreatic tissue is damaged
• Exocrine pancreatic dysfunction can present as malabsorption (steatorrhea, weight loss)
• Endocrine pancreatic dysfunction can present as diabetes (polyuria/polydipsia) 

Pathophysiology

• The pain associated with pancreatitis is due to inflammation, swelling, and stretching of the pancreatic capsule
• Peripancreatic fluid is thought to be the result of rupture or leaking of fluid from the pancreatic ducts, and this fluid is sterile and will likely resolve spontaneously - if it doesn't it may turn into a pseudocyst with a well-defined wall
• Hypercalcemia can lead to pancreatitis via premature activation of digestive enzymes within the pancreas, direct pancreatic cellular damage, and calcium salt deposition in the pancreatic ducts leading to reduced flow
• Pancreatitis can lead to hypocalcemia because lipase breaks down fat into fatty acids that bind to calcium in circulation leading to saponification (white, chalky deposits)
• Hypertriglyceridemia can lead to pancreatitis via the development of toxic metabolites from elevated free fatty acids, increased blood viscosity, and endothelial damage (leading to ischemia and increased capillary leak)

Etiology and Risk Factors

• In general, most scoring systems for acute pancreatitis are too cumbersome to calculate and only identify severe disease as it develops, limiting their clinical utility and ability to intervene using the information; moreover, they tend to perform poorly at predicting severe disease (United Euro Gastroenterol J, 2023)
• BISAP score is used to predict mortality and can be done on presentation; if 0-2 mortality is <2% and if 3-5 mortality is >15%
• The Modified Marshall Score can be used to assess for organ dysfunction, and the BISAP (Beside index of severity of acute pancreatitis) score can be used to estimate in-hospital mortality
• The RANSON score was historically used to estimate the severity of pancreatitis and associated prognosis, however, its use is limited by the inclusion of uncommonly collected labs and the need to repeat an assessment after 48 hours
• Hct >44 and BUN >20 are independent predictors of severe pancreatitis and mortality, respectively. This is likely because it implies hemoconcentration and that there is already early fluid sequestration in the pancreas
• Pancreatitis can happen after ERCP in 5-10% of cases - this can be from trauma during ductal manipulation, potential disruption of the sphincter of Oddi, and increased pressures or direct chemical injury from contrast injection; meta-analyses have shown that rectal NSAIDs can help to prevent the development of pancreatitis (Ensosc Int Open, 2019)
• Congenital malformations such as pancreas divisum or an annular pancreas can increase the risk of pancreatitis

Clinical Presentation and Diagnosis

• Diagnosis via the Revised Atlanta Classification (RAC) - 2 of 3 - consistent clinical presentation (acute, severe epigastric pain, N/V, etc.), lipase (or amylase) >3x ULN, characteristic imaging evidence
• The classic pain associated with pancreatitis involves radiation to the back (the pancreas is a retroperitoneal organ), worsening with meals (release of digestive enzymes, increased blood flow, and inflammation to the area) and when lying supine, and relief with leaning forward  (increase/decrease pressure on pancreas)
• Patients will often present with fever, leukocytosis, and other SIRS criteria without any underlying infection - be judicious with antibiotics
• Cullen and Grey Turner signs are caused by localized hemorrhage within the pancreas, diffusion of blood along the peritoneal planes, and gravity causing migration to the periumbilical (Cullen), and retroperitoneal (Grey Turner) areas; their presence should imply severe pancreatitis and usually don’t present for several days
• Lipase is ~90% sensitive and specific for pancreatitis and there is not much role for amylase anymore; the negative LR if lipase is not increased is -0.01. In other words, if lipase is not elevated it's almost certainly not acute pancreatitis.
• The level of lipase elevation does not correlate with either the severity of pancreatitis or the risk of developing complications
• Lipase elevation happens within ~6 hours in acute pancreatitis and can be elevated for weeks; there is no value in rechecking the level to trend disease progression
• Lipase may be normal in chronic pancreatitis
• Lipase may also be elevated in renal failure, cholecystitis, appendicitis (local inflammation affects the pancreas), and gastroenteritis
• An elevated ALT >150 has a high (95%) positive predictive value for biliary pancreatitis (Am J Gastroenterol, 1994)
• Amylase can also be elevated in parotitis
• A CRP >150 mg/dL can indicate severe pancreatitis and some guidelines recommend checking daily for the first 3 days; an elevated level on day 3 is a prognostic factor
• Triglycerides may be falsely low in patients presenting with pancreatitis due to a fasting state
• A CT does not need to be ordered if the first RAC two criteria are met and there is low concern for associated complications of pancreatitis
• CTAP findings can include enlarged pancreatic parenchyma with edema and fat stranding, and peripancreatic edema. Findings in chronic pancreatitis may also include pancreatic calcifications
• A RUQUS is valuable for diagnosing gallstone disease (directly visualizing cholelithiasis or indirectly via seeing a dilated biliary tree) but the sensitivity for acute pancreatitis is low often due to poor visibility from the presence of bowel gas
• Guidelines do not all agree on the aspiration of peripancreatic fluid collections; in general, it should mostly be done for cultures to guide antibiotic selection

Treatment

• Severe pancreatitis is treated like septic shock with resuscitation. Historically patients received 200-300cc/hr for the first 24 hours resulting in a positive fluid balance of 5+ liters on the first day of admission to protect end-organ perfusion. Recent data (WATERFALL Trial) suggests more conservative fluid administration is just as efficacious, but leads to fewer complications including volume overload and pulmonary edema
• PCAs can be considered for pain management, however, their utilization may lead to worse outcomes including increased length of stay and time to enteral nutrition
• Patients overall will benefit from early enteral nutrition. Historically there was concern feeding patients would stimulate the pancreas to dump all of the digestive enzymes and lead to liquefactive necrosis, and thus parenteral nutrition was preferred. However, this is largely a myth - enteral nutrition is associated with decreased mortality, organ failure, systemic infections, and the need for surgery. The proposed reason for this is that enteral feeds prevent gastrointestinal dysmotility, permeability (and thus edema and bacterial translocation)
• ERCP in pancreatitis is not urgent unless that patient has evidence of concomitant cholangitis, in which case it should be done within 24 hours
• Patients with hypertriglyceridemia are treated with insulin in the acute setting (if >1000 - the goal is to get it to less than 500). Insulin decreases lipolysis (inhibits hormone-sensitive lipase), enhances triglyceride clearance (activation of lipoprotein lipase), and reduces hepatic triglyceride production. Patients may need to be given dextrose as well.
• Patients with AIP are treated with steroids; repeat episodes are treated with immunosuppressive agents
• Patients with gallstone pancreatitis should have a cholecystectomy once they have recovered; the recurrence without surgery is 25-30%

Complications

• Complications are often not seen on imaging until a few days after the start of pancreatitis - necrotizing pancreatitis, abscess (now referred to as walled-off necrosis given the fluid collections are usually sterile), pseudocyst, and pancreatic hemorrhage are all complications to be aware of
• Peripancreatic fluid collections turn into pancreatic pseudocysts and acute necrotic collections become walled-off necrosis if either persists and develop a well-defined wall
• ~30% of patients with pancreatic necrosis will develop an infection - it will most commonly happen after 10 days of pancreatitis symptoms
• Procalcitonin may be useful for ruling out infected pancreatic necrosis - if low, it is very unlikely that the patient has an infection (according to the WSES 2019 guidelines)
• Imaging may show gas on CT in infected necrosis
• Infected pancreatic necrosis is treated with cefepime and metronidazole or carbapenem monotherapy for at least 4 weeks, adjusting based on aspiration cultures
• Pancreatic pseudocysts may need drainage or excision given only ~40% resolve spontaneously - however, necrotic collections are frequently misdiagnosed as pseudocysts because distinguishing between solid and liquid content on CT is challenging, and these necrotic collections cannot be drained
• Aggressive fluid administration in the setting of acute pancreatitis (a state with a proclivity for third-spacing fluid) can lead to abdominal compartment syndrome - look for distention, pain out of proportion to exam, and oliguria indicating renal compromise
• The duodenal and splenic blood vessels are most commonly affected in pancreatitis and can be eroded by severe inflammation, leading to hemorrhage

Reviews

• Acute Pancreatitis: A Review (JAMA, 2021)
• Acute Pancreatitis (NEJM, 2016)

Trials

• WATERFALL Trial - Aggressive (20 ml/kg bolus + 3 ml/kg/hr) vs Non-Aggresive (10 ml/kg bolus + 1.5 ml/kg/hr) fluid resuscitation in acute pancreatitis - fluid overload resulted in 20.5% vs 6.3% of patients but no difference in the development of moderately severe or severe pancreatitis (NEJM, 2022)

Other Literature

• Enteral versus parenteral nutrition for acute pancreatitis (Cochrane, 2010)
• A Critical Evaluation of Laboratory Tests in Acute Pancreatitis (Am J Gastroenterol, 2002)

Blogs and Summaries

• Clinical Problem Solvers - Acute Pancreatitis Illness Script
• Internet Book of Critical Care - Pancreatitis
• Radiopaedia - Imaging Findings in Acute Pancreatitis
• Pathway Guidelines Summary - Acute Pancreatitis

Clinical Calculators

• MD Calc - BISAP - predict mortality
• QxMD - Modified Marshall Score - assess for organ dysfunction
• MD Calc - APACHE II Score - used in ICU setting to determine severity
• MD Calc - RANSON - severity and prognosis; impractical as done after 48 hours