Acute Pancreatitis in Adults

Acute Pancreatitis in Adults
Overview and Recommendations
Background
● Acute pancreatitis is a rapid onset in ammatory process of the pancreas which can a ect multiple
organ systems.
● Severity can be assessed according to the revised Atlanta criteria.
⚬ Revised Atlanta criteria assess the following factors:
– local complications such as pseudocyst, pancreatic necrosis.

– organ failure such as acute respiratory failure (partial pressure of oxygen to fraction of inspired
oxygen ratio < 400), shock (systolic blood pressure ≤ 90 mm Hg) and/or renal failure (creatinine
≥ 1.4 mg/dL).
⚬ Mild acute pancreatitis is de ned as the absence of:
– any extrapancreatic organ failure, including failure in respiratory, cardiovascular, and renal
systems
– local or systemic complications.
⚬ Moderately severe acute pancreatitis is de ned as nding of complications, such as:
– peripancreatic uid collection or peripancreatic necrosis

– systemic complications without persistent organ failure.
⚬ Severe acute pancreatitis is de ned as the presence of organ failure that persists > 48 hours.
● The most common causes of acute pancreatitis are gallstones and signi cant alcohol use. Alcoholic
pancreatitis usual occurs in the setting of chronic heavy consumption, usually more than 5 years of
alcohol consumption above > 50 g/day.
● Other causes of acute pancreatitis include drugs, hypertriglyceridemia, trauma including post-
endoscopic retrograde cholangiopancreatography (ERCP), and infections.
● Prevention strategies are available for certain causes of acute pancreatitis including gallstones and
hypertriglyceridemia. See the Prevention of Acute Pancreatitis topic for detailed information.
Evaluation
● Establishing a diagnosis of acute pancreatitis:
⚬ Typical features of acute pancreatitis include:
– acute epigastric or left upper quadrant abdominal pain

– pain which worsens in the supine position or radiates to the back
– associated nausea and vomiting
⚬ Obtain serum amylase and lipase if acute pancreatitis is suspected.

⚬ Diagnose acute pancreatitis if ≥ 2 of:
– abdominal pain consistent with pancreatitis

– serum amylase and/or lipase > 3 times upper limit of normal
– characteristic ndings from abdominal imaging (ultrasound recommended as rst line)
⚬ If the diagnosis is uncertain or there is failure to improve clinically within 48-72 hours obtain
contrast-enhanced computed tomography (CECT) or magnetic resonance imaging (MRI) (Strong
recommendation).
● Additional testing
⚬ Obtain blood urea nitrogen (BUN), creatinine, liver function tests, albumin, glucose, lactate
dehydrogenase (LDH), white blood cell count, hematocrit, calcium, and arterial blood gases to
identify related comorbidities and complications, and assess severity.
⚬ Obtain serum triglyceride level if no history of gallstones or signi cant alcohol use (Weak
recommendation).
⚬ Imaging in patients with acute pancreatitis:
– Obtain abdominal ultrasound in all patients with acute pancreatitis (Strong recommendation) to
assess for gallstones.
– Consider endoscopic ultrasound (EUS) or magnetic resonance cholangiopancreatography
(MRCP) if choledocholithiasis is highly suspected in the absence of cholangitis and/or jaundice
(Weak recommendation).
● If infected necrosis is suspected, either perform a CT-guided ne-needle aspiration for Gram stain and
culture, or provide empiric antibiotics (Strong recommendation).
● Perform endoscopic retrograde cholangiopancreatography (ERCP) within 24 hours if there is

concurrent acute cholangitis with obstruction (Strong recommendation). ERCP is not needed if there is
no evidence of ongoing biliary obstruction (Strong recommendation).
● Consider MRCP and/or EUS study to evaluate for pancreatic or extrapancreatic tumor as possible
cause of acute pancreatitis in patients > 40 years old (Weak recommendation).
● Consider alternative causes of acute abdominal pain such as gall stones, kidney stones, or
appendicitis.
Management
● Treatment setting:
⚬ Most episodes of acute pancreatitis are mild, needing only brief admission to a general medicine
unit
⚬ Admit the patient to an intensive care unit if there is organ failure (Strong recommendation), or
other signs and symptoms of a severe disease including hypoxia, tachypnea, delirium, signi cant
gastrointestinal bleeding, hypotension, or systemic in ammatory response syndrome (SIRS).
● Provide aggressive hydration (such as lactated Ringer's solution 250-500 mL/hour) (Strong
recommendation)
⚬ Reassess uid requirements at frequent intervals within 6 hours of admission and for the next 24-
48 hours to achieve decrease in blood urea nitrogen (Strong recommendation).
⚬ Adequate uid resuscitation should maintain urine output ≥ 0.5 mL/kg/hour without renal failure.
● Provide analgesia, which is critically important, but there is insu cient evidence to suggest optimal
drug selection.
● Ensure adequate nutrition.
⚬ In mild acute pancreatitis, consider starting oral feeding as soon as the patient is free from nausea,
vomiting, and abdominal pain (Weak recommendation).
⚬ In severe acute pancreatitis, provide enteral nutrition instead of parenteral nutrition (Strong
recommendation).
● In severe acute pancreatitis:
⚬ Do not give prophylactic antibiotics, including for patients with sterile necrosis (Strong
recommendation).
⚬ Prescribe antibiotics for extrapancreatic infection (Strong recommendation).
⚬ Insulin may be required temporarily.
● Perform endoscopic retrograde cholangiopancreatography (ERCP) within 24 hours for patients with
gallstone pancreatitis with cholangitis and within 72 hours in patients with high suspicion of persistent
common bile duct stone (Strong recommendation).
● Do not perform drainage or debridement for asymptomatic pancreatic pseudocysts or necrosis

(regardless of size or location) (Strong recommendation).
● if infected necrosis is suspected, obtain a computed tomography (CT)-guided ne-needle aspiration

for Gram stain and culture to guide antibiotic selection, or provide empiric antibiotics with 1 of the
following (Strong recommendation):
⚬ imipenem-cilastatin 500 mg IV every 8 hours
⚬ meropenem 1 g IV every 8 hours
⚬ cipro oxacin 400 mg IV every 12 hours plus metronidazole 500 mg IV every 8 hours
● If performing necrosectomy for symptomatic infected necrosis, use minimally invasive methods if
feasible (Strong recommendation).
● Monitor for systemic complications, especially pulmonary, cardiovascular and renal complications.
● In patients with gallstones, perform cholecystectomy (Strong recommendation).
⚬ In mild cases, perform before discharge.

⚬ In severe cases perform after in ammation and uid collections resolve or stabilize, which may or
may not occur before discharge.
● To decrease risk of recurrent acute pancreatitis, treat alcohol abuse disorders and triglyceride levels >
1,000 mg/dL (11.3 mmol/L).
Related Summaries
● Acute Pancreatitis in Children
● Chronic Pancreatitis
● Prevention of Acute Pancreatitis
● Causes of Acute Pancreatitis
● Autoimmune Pancreatitis
Hospitalist Focused Content

Content referenced with “Consensus” in Hospitalist Focused Content is supported by a combination of
the best available evidence and expert opinion put forth by a panel of Hospitalists.
Panel participants:
● Vijay Duggirala, MD: Clinical Assistant Professor, The Ohio State University College of Nursing; Clinical
Assistant Professor, The Ohio State University College of Medicine; Hospitalist, Director of Consult
Services and Director of Quality & Patient Safety, Division of Hospital Medicine, The Ohio State Wexner
Medical Center; Ohio, United States
● Dr. Duggirala declares no relevant nancial con icts of interest.
● Chi Huang, MD: Executive Medical Director of General Medicine and Hospital Medicine Shared
Services, Wake Forest Baptist Health System; Section Chief, Hospital Medicine, Wake Forest Baptist
Medical Center; Associate Professor of Internal Medicine, Wake Forest Medical School; North Carolina,
United States
● Dr. Huang declares no relevant nancial con icts of interest.
● Richard Rothman, MD: Chair and Physician Advisor, Department of Hospital Medicine, Cleveland Clinic
India River Hospital; Florida, United States
● Dr. Rothman declares no relevant nancial con icts of interest.
● Andrés J. Solorza, MD: Assistant Clinical Professor, Tufts University; Chair-Person, Department of
Hospital Medicine, Lahey Hospital and Medical Center; Massachusetts, United States
● Dr. Solorza declares no relevant nancial con icts of interest.
● Nestor G. Tarragona, MD, FHM, FACP: Assistant Professor of Medicine, Tufts University School of
Medicine; Vice Chairperson, Division of Hospital Medicine, Lahey Hospital and Medical Center; Medical
Director for Latin America, Teladoc Health; Massachusetts, United States
● Dr. Tarragona declares no relevant nancial con icts of interest.
● Yoania Quintana-Garcia, MD: Hospitalist, Cleveland Clinic Indian River Hospital; Florida, United States
● Dr. Quintana-Garcia declares no relevant nancial con icts of interest.
Admission Checklists
General Admission Checklist
● Determine code status Consensus
● Establish IV accessConsensus
● Determine appropriate treatment settingConsensus
● Diet should be nothing per mouth (NPO) on admissionConsensus
● Consider deep vein thrombosis (DVT) prophylaxis if indicated (Chest 2012 Feb;141(2 Suppl):e195S
full-text )
● Communicate with outpatient primary care provider (PCP) to obtain:Consensus
⚬ Outpatient advanced directives

⚬ Problem list
⚬ Reconciled medication list
⚬ Medical and surgical history
⚬ List of other healthcare providers involved
● Engage in collaborative care management with the PCP during hospital stayConsensus
Admission Checklist for Patients With Acute Pancreatitis
● Establish diagnosis using accepted criteria and ensure no other causes of presentation criteria
● Diet should be nothing per mouth (NPO) on admission; in mild cases of acute pancreatitis (AP) oral
feedings may be initiated early if no associated nausea or vomiting (ACG Conditional
recommendation, Moderate-quality evidence) 1
● Check labs including complete blood count (CBC), renal function, liver enzymes, bilirubin, amylase,
and lipase in all suspected cases
● Blood urea nitrogen (BUN), creatinine, liver function tests, albumin, glucose, lactate dehydrogenase
(LDH), white blood cell count, hematocrit, calcium, and arterial blood gases may identify related
comorbidities and complications, and inform prognosis
● Obtain imaging if diagnosis is unclear, otherwise computed tomography, magnetic resonance

imaging, and ultrasound is not necessary on admission but should be considered if there is no
improvement in 48-72 hours
● Initiate early aggressive uid resuscitation with crystalloid ; titrate to urine output, and to achieve a
decrease in BUN; re-evaluate volume status frequently, at minimum every 6 hours and bolus as
needed for persistent hypovolemia; in patients with renal insu ciency or acute renal failure balanced,
crystalloids such as lactated Ringer solution may be preferable (N Engl J Med 2018 Mar 1;378(9):829
full-text , N Engl J Med 2018 Mar 1;378(9):819 full-text , J Hosp Med 2019 Mar;14(3):172 )
● Provide analgesia for patient comfort; typically, narcotics are used 5 , 6 ; avoid nonsteroidal anti-
in ammatory drugs (NSAIDs) except in mild pancreatitis due to the risk for worsening renal
dysfunctionConsensus
● Do not start antibiotics on admission for a new episode of pancreatitis for prophylaxis or treatment
even if necrosis is identi ed (ACG Strong recommendation, Moderate-quality evidence; AGA
Conditional recommendation, Low-quality evidence) 1 , 4 ; they can be used if another source of
infection is suspected or con rmed
● Etiology evaluation:
⚬ Initiate workup for etiology including evaluation for gallstones (abdominal ultrasound in most
patients) (ACG Strong recommendation, Low-quality evidence) 1 and history for alcohol usage
(ACG Conditional recommendation, Moderate-quality evidence) 1 and new or high-risk
medications in all patients with new-onset pancreatitis (see Causes of Acute Pancreatitis for
additional information)
⚬ Consider additional etiologic workup such as triglyceride levels, evaluation for malignancy,
autoimmune, genetic testing, etc. in patients without an etiology identi ed
⚬ Ensure urgent endoscopic retrograde cholangiopancreatography (ERCP) (within 24 hours) in
patients with evidence of cholangitis but not in those without ongoing evidence of biliary
obstruction (Cochrane Database Syst Rev 2012 May 16;(5):CD009779 )
● Initiate nutrition with enteral feeding (either by oral or by tube feeding) whenever possible and ideally
within 72 hours:
⚬ In mild acute pancreatitis, oral feeding may be started immediately if asymptomatic(ACG
Conditional recommendation, Moderate-quality evidence) 1

⚬ In severe acute pancreatitis or patients not expected to be able to eat within a week, enteral
nutrition recommended (AGA Strong recommendation, Moderate-quality evidence) 4
● In patients with symptomatic necrosis/cysts, avoid necrosectomy in the acute setting, ideally until at
least 30 days from the initial episode (ACG Strong recommendation, Low-quality evidence) 1 ;
asymptomatic necrosis and/or cysts do not require intervention (ACG Moderate recommendation,
High-quality evidence) 1
● Cholecystectomy should be performed for gallstone pancreatitis if gallstones still in gallbladder prior
to discharge in mild cases (ACG Moderate recommendation, Moderate-quality evidence) 1 and after
active in ammation and uid collections resolve (ACG Strong recommendation, Moderate-quality
evidence) 1 or stabilize (> 2 weeks) in severe cases (JAMA Surg 2018 Nov 1;153(11):1057 full-text
)
● Consider treating hypertriglyceridemic pancreatitis with agents such as insulin, IV heparin, and
plasmapheresis based on limited data from case series
Treatment Setting
Most patients with pancreatitis including nearly all with a rst episode should be admitted to the hospital
for management.Consensus
Stable patients with uncomplicated pancreatitis can be admitted to the general ward, provided that
regular vital signs and close urine output monitoring are available.
Consider intermediate care unit for patients at high risk of deterioration, such as:
● Elderly patients
● Patients with obesity
● Patients needing large volume of resuscitation
● Patients with pancreatic necrosis
● Reference - Lancet 2008 Jan 12;371(9607):143
Admit patients with organ failure to intensive care unit (ICU) or intermediary care setting whenever
possible (ACG Strong recommendation, Low-quality evidence). 1
Admission to ICU also indicated if severe disease, including presence of: 1 , 3 , 5 , 6

● Hypoxia
● Tachypnea
● Delirium
● Signi cant gastrointestinal bleeding
● Features of substantial third-space loss (hypotension, tachycardia, azotemia, or signi cant

hemoconcentration)
● Evidence of systemic in ammatory response syndrome (SIRS)
Consultation and Referral
Consider urgent consultation with gastroenterologist for all patients with cholangitis or evidence of
biliary obstruction for consideration of ERCP.Consensus
Consider consultation with gastroenterologist for any patient with moderate-to-severe pancreatitis to
assist in management and less-invasive intervention if required for pancreatic necrosis or
pseudocysts.Consensus
Surgical consultation for any patient with uncomplicated mild pancreatitis due to gallstones to consider
same-admission cholecystectomy; for patients with moderate-severe pancreatitis, this should typically be
arranged as an outpatient after in ammation subsides. ( 1 , Am J Gastroenterol 2019 Aug;114(8):1322 )
Surgical intervention may also be required for abdominal compartment syndrome (rare) or failed less-
invasive methods of drainage/debridement for necrosis. (Pancreatology 2013 Jul;13(4 Suppl 2):e1 )
Interventional radiology assistance may be indicated for management or sampling of pancreatic

necrosum or pseudocysts. 5 , 6
Consider endocrinology consultation in patients with hypertriglyceridemia-induced pancreatitis for

insulin therapy, or for treatment of new diabetes.Consensus
Consider consultation with nephrologist for severe renal injury from pancreatitis.Consensus
Consider consultation with pheresis team for hypertriglyceridemia (institution-dependent).Consensus
Social work or other psychological counseling for alcohol-induced pancreatitis. 5
Discharge Planning
Start discharge planning on day one. (J Hosp Med 2013 Aug;8(8):421 )
Communicate with outpatient providers about hospital course and ensure an outpatient plan to manage
any complications from the pancreatitis.Consensus
Ensure any pancreatitis-caused organ failure and disease-related pain is stabilized or resolved.Consensus
Counsel patient on the expected course based on severity and whether recovery of normal pancreatic
function is expected.Consensus
Counsel all patients to avoid alcohol intake and cease smoking as both of these may increase the risk of
recurrent pancreatitis. 3 , 5
Discontinue any medication implicated in causation of pancreatitis when possible.Consensus

If a patient is requiring ongoing tube feeds or narcotic analgesia, identify an outpatient provider to
transition care if relevant.Consensus
Ensure diet or stable enteral nutrition is well tolerated.Consensus
Discharge Checklist
General Discharge Checklist
● Ensure communication with outpatient providers about hospital courseConsensus
Discharge Checklist for Patients With Acute Pancreatitis
● Consider referrals as appropriate for any newly developed complications (for example, renal failure or
diabetes) as a result of the pancreatitisConsensus
● Consider dietitian consultation for low-fat diet to be maintained during convalescenceConsensus
● If there is a new diagnosis of diabetes (related to pancreatic necrosis), ensure patient has appropriate
supplies and educationConsensus
● Ensure outpatient specialty follow-up as appropriate including gastroenterologist, typically within 30-
60 daysConsensus
● Ensure repeat procedure/evaluation scheduled for any patient with drains or linesConsensus
● Referral for cholecystectomy if gallstones present and unable to perform in-hospital 1
● Ensure close primary care follow-up within 1 week of dischargeConsensus
● Communicate any pending workup for etiology with following providersConsensus
● Ensure pain is controlled with only minimal oral narcotic requirement if anyConsensus
● Referral to alcohol cessation resources as appropriate 3 , 5
● Counsel to stop smoking if applicable and provide resources to do so 3 , 5
General Information
Description
● acute, in ammatory condition of the pancreas which can a ect multiple organ systems, causing local
or systemic complications and organ failure 4
Definitions
● disease onset de ned as time of onset of abdominal pain 2
● chronic pancreatitis de ned as progressive in ammation of pancreas with destruction of pancreatic

secretory cells leading to malnutrition and diabetes
Types
Revised Atlanta Criteria
● mild acute pancreatitis de ned as both 1 , 2
⚬ absence of organ failure

⚬ absence of local or systemic complications, such as pancreatic necrosis
● moderately severe acute pancreatitis characterized by presence of either 1 , 2
⚬ transient organ failure (organ failure resolving in ≤ 48 hours)

⚬ local or systemic complications without persistent organ failure
● severe acute pancreatitis (occurs in 15%-20%) 1 , 2
⚬ de ned as persistence of organ failure (single or multiple) for > 48 hours

⚬ in rst 48 hours, cannot distinguish between severe disease which is temporary or severe acute
pancreatitis which is developing
⚬ organ failure de ned as modi ed Marshall score > 2 and must be recorded ≥ once during each of 3
consecutive days in any of following systems
– respiratory system (partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio
[PaO2 mm Hg/FiO2]) (see PaO2/FiO2 ratio calculator)
● score 0 if > 400 mm Hg

● score 2 if 301-400 mm Hg
– cardiovascular system (systolic blood pressure)
● score 0 if > 90 mm Hg
● score 1 if < 90 mm Hg and uid responsive
● score 2 if < 90 mm Hg and not uid responsive
● score 3 if < 90 mm Hg and pH < 7.3
● score 4 if < 90 mm Hg and pH < 7.2
– renal system (serum creatinine levels by micromol/L or mg/dL)
● score 0 if < 134 or < 1.4

● score 1 if 134-169 or 1.4-1.8
● score 2 if 170-310 or 1.9-3.6
● score 3 if 311-439 or 3.6-4.9
● score 4 if > 439 or > 4.9
⚬ multisystem organ failure de ned as ≥ 2 of respiratory, cardiovascular, and renal organ systems
failing over the same 2- to 3-day period
Morphologic (Image-based) Classification
● interstitial edematous pancreatitis (IEP) 2
⚬ di use or localized enlargement of the pancreas

⚬ normal, homogeneous enhancement of pancreatic parenchyma
⚬ peripancreatic fat usually shows some inflammatory changes of haziness or mild stranding
⚬ usually resolves within rst week
● necrotizing pancreatitis 2
⚬ presence of necrosis involving both the pancreas and peripancreatic tissues (most common)
⚬ necrosis of only the peripancreatic tissue (less common, worse prognosis compared with patients
with IEP)
⚬ necrosis of only pancreatic parenchyma (rare)
⚬ necrosis may be
– sterile
– infected
● rare in rst week

● no absolute correlation between extent of necrosis and risk of infection and duration of
symptoms
● infection presumed if extraluminal gas present in nonenhancing area(s) on contrast-
enhanced computed tomography (CECT) (virtually pathognomonic for presence of gas-
forming organism without or with perforation)
● diagnosis based de nitively only on image-guided, ne-needle aspiration (FNA) with positive
Gram stain and culture
● may evolve from solid necrosis early in course to variable liquefaction and variable
reabsorption
● if not completely reabsorbed, may persist as area of walled-o pancreatic necrosis (WOPN)
which may be
⚬ symptomatic
⚬ cause of pain or mechanical obstruction of duodenum and/or bile duct
● see classi cation of pancreatic local complications in Diagnosis for additional information and images
Epidemiology
Incidence/Prevalence
● incidence reported varies worldwide, but rising incidence consistent with increasing rates of
worldwide obesity and obesity-related complications including gallstones and diabetes 3
STUDY
● SUMMARY
global incidence estimates of acute pancreatitis 34 cases per 100,000 person-years and 1.6
deaths per 100,000 person-years
SYSTEMATIC REVIEW: Lancet Gastroenterol Hepatol 2016 Sep;1(1):45
Details
⚬ based on systematic review of observational studies
⚬ systematic review of 48 population-based cohort studies with total of 296.000,000 individuals and
119,000 patients with pancreatic diseases
– pancreatic cancer (35 studies)
– acute pancreatitis (10 studies)
– chronic pancreatitis (3 studies)
⚬ global estimates of incidence and mortality were 33.74 cases per 100,000 person-years and 1.6
deaths per 100,000 person-years for acute pancreatitis
⚬ in subgroup analysis based on World Health Organization (WHO) regions incidence of acute
pancreatitis signi cantly higher in American region than in European and Western Paci c regions
⚬ no di erence in incidence of acute pancreatitis between men and women
⚬ Reference - Lancet Gastroenterol Hepatol 2016 Sep;1(1):45
STUDY
● SUMMARY
incidence of acute pancreatitis among privately insured patients remained stable at 12 per
100,000 persons in children, and decreased from 124 to 111 per 100,000 persons in adults during
2007-2014 in United States
COHORT STUDY: Gastroenterology 2018 Aug;155(2):469
Details
⚬ based on cohort study
⚬ 141,017,841 patients aged 0-64 years who were privately insured and had inpatient and outpatient
medical insurance claims data available in 2007-2014 in United States were analyzed
⚬ 0.25% had acute pancreatitis
⚬ incidence of acute pancreatitis
– remained stable at 12.3 per 100,000 persons from 2007 to 2014 in children and adolescents ≤ 18
years old
– decreased from 123.7 per 100,000 persons in 2007 to 111.2 per 100,000 persons in 2014 in
adults aged 19-64 years (p = 0.04)
⚬ Reference - Gastroenterology 2018 Aug;155(2):469 , and commentary can be found in
Gastroenterology 2019 Jan;156(1):287
⚬
DynaMed Commentary
The study authors were criticized in a commentary for methodologic issues, which they
credibly responded to, and in their reply hypothesize that reduced rates of tobacco use during
the follow-up time period may have reduced the incidence of acute pancreatitis.
STUDY
● SUMMARY
incidence of hospital admissions for acute pancreatitis in United States increased 16.4% from
2002 to 2012
Pancreas 2017 Apr;46(4):482
Details
⚬ based on retrospective cohort study
⚬ 2,016,045 adult inpatient admissions with diagnosis of acute pancreatitis from Nationwide
Inpatient Sample were reviewed
⚬ compared to 2002, a reported 16.4% increase in hospital admissions for acute pancreatitis in 2012
⚬ Reference - Pancreas 2017 Apr;46(4):482 full-text
● incidence of acute pancreatitis during pregnancy 1 case per 1,000 to 10,000 pregnancies
⚬ in cases of acute pancreatitis reported during and after pregnancy,
– 12% occur in rst and second trimesters

– 50% occur in third trimester
– 38% occur in early postpartum period
⚬ reported causes during pregnancy
– gallstones in > 65%

– alcohol abuse in 5%-10%
– idiopathic in 15%
– familial hypertriglyceridemia-induced pancreatitis in 5%
⚬ Reference - J Perinatol 2014 Feb;34(2):87
● incidence of hospital discharge diagnosis of alcoholic pancreatitis 49.2 per 100,000 persons in United
States in 1988-2004 (Arch Intern Med 2008 Mar 24;168(6):649 )
● incidence rates reported with HIV infection
⚬ range between 6.1 and 140 cases per 1,000 person-years before introduction of highly e ective
antiretroviral therapy (Asian Pac J Trop Biomed 2013 Jun;3(6):422 full-text )
⚬ 3.6 cases per 1,000 person-years after introduction of highly e ective antiretroviral therapy in era
with fewer patients taking nucleoside reverse transcriptase inhibitors (NRTIs), such as stavudine
(AIDS Patient Care STDS 2008 Feb;22(2):113 full-text )
Risk Factors
● causes and risks for acute pancreatitis include 3 , 6
⚬ gallstones (most common cause of acute pancreatitis)

⚬ alcohol abuse
⚬ medications, for example azathioprine, didanosine, estrogens, furosemide, pentamidine,
sulfonamides, tetracycline, valproic acid
⚬ hypertriglyceridemia
⚬ blunt or penetrating abdominal trauma
⚬ postendoscopic retrograde cholangiopancreatography (ERCP)
⚬ genetic predisposition
⚬ morbid obesity
⚬ type 2 diabetes
⚬ smoking
⚬ toxins
⚬ see also Causes for Acute Pancreatitis
STUDY
● SUMMARY
cigarette smoking may be associated with increased risk of acute pancreatitis
SYSTEMATIC REVIEW: PLoS One 2015;10(4):e0124075 | Full Text
Details
⚬ systematic review of 22 observational studies (6 cohort, 14 case-control, and 2 cross-sectional
studies) evaluating e ect of cigarette smoking on development of pancreatitis
⚬ compared to never smoking, increased risk of acute pancreatitis associated with
– ever smoking (relative risk [RR] 1.51, 95% CI 1.1-2.07) in analysis of 8 studies
– current smoking (RR 1.42, 95% CI 1.08-1.87) in analysis of 9 studies (results limited by signi cant
heterogeneity)
– former smoking (RR 1.22, 95% CI 0.99-1.52) in analysis of 7 studies (results limited by signi cant
heterogeneity)
⚬ Reference - PLoS One 2015;10(4):e0124075 full-text
Factors Not Associated with Increased Risk
● pregnancy - coexistence of additional factors usually explain higher frequency among pregnant
women, and include
⚬ increased biliary sludge and gallstones
⚬ secondary hypertriglyceridemia
⚬ prepregnancy dyslipidemia
⚬ Reference - J Perinatol 2014 Feb;34(2):87
Etiology and Pathogenesis
Causes
● most common causes in general population 3 , 6
⚬ gallstones (about 40% of cases)

⚬ alcohol abuse (about 35% of cases)
⚬ medications (about 2% of cases)
⚬ hypertriglyceridemia (about 1%-4% of cases)
⚬ blunt or penetrating abdominal trauma (about 1.5% of cases)
⚬ postendoscopic retrograde cholangiopancreatography (ERCP) (5%-10% of patients having ERCP) 3
● idiopathic (about 10% of cases)
● most common causes in children
⚬ trauma and systemic diseases, especially hemolytic uremic syndrome (HUS)

⚬ biliary tract disease
● most common causes during pregnancy in United States
⚬ biliary tract disease

⚬ alcohol abuse
● other less common causes include
⚬ autoimmune disorders (including Sjogren syndrome, autoimmune hepatitis, celiac disease)

⚬ genetic causes (gene mutations)
⚬ IgG4-related disease
⚬ hypercalcemia
⚬ infection (viral, bacterial, parasitic, or fungal)
⚬ obstructive abnormalities of pancreas (including pancreas divisum or sphincter of Oddi
dysfunction)
⚬ pancreatic cancer
⚬ postsurgical procedures
⚬ toxic exposures (venom, organophosphate insecticide)
⚬ vascular abnormalities (ischemia, vasculitis)
● see Causes of Acute Pancreatitis for details
Pathogenesis
● cellular events in pathogenesis of acute pancreatitis include
⚬ pathological calcium signaling

⚬ mitochondrial dysfunction
⚬ premature trypsinogen activation within pancreatic acinar cells and macrophages
⚬ endoplasmic reticulum (ER) stress
⚬ impaired unfolded protein response
⚬ impaired autophagy
● triggers for these cellular events include
⚬ toxins, such as alcohol, nicotine and bile acids

⚬ increased pressure caused by ductal obstruction, luminal acidi cation, and ductal cell exposure to
bile acid
● central pathophysiology is injury to pancreatic acinar cells, leading to subsequent in ammatory

responses that are localized to the pancreas in milder disease or systemic in severe disease
● injury of acinar cells manifests in pathological elevation of intracellular calcium, which mediates pro-
cell death and pro-in ammatory pathways and acinar cell organelle dysfunction
⚬ pancreatic acinar cells
– synthesize, transport, store, and secrete digestive enzymes

– transport secreted digestive enzymes to the small intestine by a ductal system secreting large
amounts of bicarbonate-rich uid
⚬ pathological acinar cell organelle dysfunctions in acute pancreatitis include
– mitochondrial depolarization/dysfunction
– pathologic endoplasmic reticulum (ER) stress
– disordered endolysosomal-autophagy
⚬ acinar cell organelle dysfunctions lead to activation of inappropriate cellular and in ammatory
responses, including
– premature trypsin activation, by conversion of preformed trypsinogen to activated trypsin
– dysregulated secretion
– vacuole accumulation
– production of pro-in ammatory cytokines
– release of pro-in ammatory damage-associated molecular patterns (DAMPs) and other
in ammatory molecules by dying and necrotic acinar cells
● DAMPs released extracellularly activate in ammatory signals and exacerbate acute
in ammation locally and in distant sites
● nuclear components released from damaged and dying acinar cells additionally trigger
innate immune systems involving dendritic cells and macrophages
⚬ released trypsin causes autodigestion within and outside acinar cells, and cathepsin B release
causes necroptosis
⚬ other in ammatory stimuli which are activated by crosstalk between acinar cells and the immune
system and propagate in ammatory responses include
– elastase and phospholipase A2
– complement and kinin pathway components
– cytokines interleukin 6 and interleukin 10, and chemokine monocyte chemoattractant protein-1
(MCP1) from acinar cells, which facilitates in ammatory monocyte tra cking
– macrophage in ammatory protein 2alpha (MIP2alpha) and CXC chemokine ligand 1 (CXCL1),
which recruit neutrophils
– cytokines interleukin 1, interleukin 6, and interleukin 8 from neutrophils, macrophages, and
lymphocytes
– tumor necrosis factor
⚬ propagated local and systemic pancreatic in ammatory responses include
– tissue injury associated with innate immune activation and rapid neutrophil in ltration,
followed by macrophage recruitment
– impaired pancreatic regeneration and de-di erentiation of pancreatic epithelium by pro-
in ammatory macrophages
– activation of endothelial cells which enables leukocyte transendothelial migration leading to
release of additional tissue-damaging enzymes
– tissue injury caused by production of oxygen-derived free radicals
– release of proteins from pancreas or other organs (such as the liver) which may cause injury to
remote organs (such as lungs)
– activation of monocytes in lungs, liver and peritoneum
⚬ several gene mutations have been identi ed that have pathogenic roles in acute pancreatitis,
including
– protease serine 1
– serine protease inhibitor Kazal type 1
– chymotrypsin C
– CFTR
– claudin 2
– calcium-sensing receptor
⚬ Reference - Nat Rev Gastroenterol Hepatol 2019 Aug;16(8):479 , Gastroenterology 2019

May;156(7):1941 full-text , and Curr Opin Gastroenterol 2015 Sep;31(5):395 full-text
● disease course 2
⚬ early phase (usually within the rst week of onset)
– severity related to organ failure secondary to host’s systemic in ammatory response elicited by
tissue injury (not necessarily to extent of necrosis)
– initial state of in ammation and variable degrees of pancreatic and peripancreatic ischemia
and/or edema evolve to either
● resolution
● irreversible necrosis, liquefaction, and/or development of uid collections in and around the
pancreas
– extent of pancreatic and peripancreatic changes not directly proportional to severity of organ
failure
– organ failure related to systemic in ammatory response may
● resolve within 48 hours (known as "transient organ failure")

● persist > 48 hours (de ned as "persistent organ failure")
– cytokine cascades activated by pancreatic in ammation manifest clinically as systemic

in ammatory response syndrome (SIRS)
⚬ late phase (occurring after rst week of disease onset)
– characterized by either
● persistence of systemic signs of inflammation

● development of local complications
– persistent organ failure is main determinant of severity

– use clinical and “morphologic” criteria for classi cation of severity and its treatment
– early phase SIRS may be followed by compensatory, anti-in ammatory response syndrome
(CARS)
History and Physical
History
Chief Concern (CC)
● compatible clinical features include 1 , 4 , 6
⚬ severe epigastric or periumbilical pain
– pain may last for days

– pain worsens after eating or drinking, especially fatty foods
– pain may radiate to the back, chest, or anks
– intensity of pain usually severe, but can be variable
– pain may worsen when patient is supine
– pain typically becomes constant over time.
⚬ nausea and vomiting

⚬ indigestion
⚬ abdominal fullness
⚬ abdominal distention
⚬ frequent hiccups
⚬ patient may occasionally present with transient loss of consciousness (syncope) 6
History of Present Illness (HPI)
● disease course has 2 distinct phases 1 , 2
⚬ early phase occurs within 1 week of onset
– systemic disturbances result from local pancreatic injury

– severity during the early phase is primarily determined by presence and duration of organ
failure
● transient organ failure resolves within 48 hours
● persistent organ failure lasts for > 48 hours
⚬ late phase occurs after rst week of disease onset and may last weeks to months
– occurs only in patients with moderately-severe or severe acute pancreatitis

– marked by local complications or persistence of systemic signs of inflammation
Medication History
● ask about medications that may be causes, including 3 , 6
⚬ angiotensin-converting enzyme (ACE) inhibitors

⚬ azathioprine
⚬ estrogens
⚬ furosemide
⚬ tetracycline
⚬ 6-mercaptopurine
⚬ mesalamine
⚬ pentamidine
⚬ sulfonamide
⚬ valproate
⚬ see Causes of Acute Pancreatitis for details
Past Medical History (PMH)
● ask about history of conditions that increase risk for acute pancreatitis, including 3 , 6
⚬ previous episode of pancreatitis

⚬ biliary-colic type pain or cholelithiasis (gallstones)
⚬ other gastrointestinal disorders (Crohn disease, duodenal ulcers)
⚬ recent procedures
– abdominal or cardiac surgery

– endoscopic retrograde cholangiopancreatography (ERCP)
⚬ recent abdominal trauma

⚬ infection (including HIV infection)
⚬ toxin exposure (scorpion or snake bites)
⚬ autoimmune pancreatitis
⚬ cystic brosis (CF)
⚬ diabetes mellitus
Family History (FH)
● ask about family history of pancreatitis (usually autosomal dominant) 6
● ask about family history of hypertriglyceridemia 6
Social History (SH)
● ask about 1 , 3 , 6
⚬ alcohol use (including recent binge)

⚬ smoking history
⚬ travel history (possible infectious exposures)
⚬ exposures (scorpion venom, organophosphates)
Physical
General Physical
● general physical examination ndings may include 6
⚬ hypotension
⚬ tachycardia
⚬ tachypnea
⚬ diaphoresis
⚬ fever
● if severe disease, patient may present with altered mental status 6
Skin
● ecchymosis due to exudate from necrotic pancreatic tissue 6
⚬ may appear as bruising and edema in the subcutaneous tissue around the umbilicus (Cullen sign)
⚬ may appearing over the anks (Grey Turner sign)
● jaundice may be present 6
Lungs
● listen for signs of pleural e usion 1
⚬ dullness to percussion
⚬ diminished breath sounds
Abdomen
● abdominal examination typically reveals notable tenderness to palpation, especially in the epigastric
region
● guarding, signs of peritoneal irritation, distension, or rigidity 6
● decreased bowel sounds, typically 6
Neuro
● signs of hypocalcemia 5
⚬ muscle spasm
⚬ Chvostek's sign (tapping on facial nerve leading to twitching of facial muscles)
⚬ Trousseau's sign (carpopedal spasm with in ated blood pressure cu )
Diagnosis
Making the Diagnosis
● diagnosis of acute pancreatitis requires ≥ 2 of the following criteria (ACG Strong recommendation,
Moderate-quality evidence) 1 , 2 )
⚬ abdominal pain consistent with acute pancreatitis
– severe epigastric or periumbilical pain
● worsens after eating or drinking, especially fatty foods

● may radiate to the back, chest, or anks
● intensity of pain usually severe, but can be variable
● pain typically becomes constant over time.
● pain may last for days
⚬ serum lipase and/or amylase > 3 times upper limit of normal

⚬ ndings from abdominal imaging characteristic of acute pancreatitis, including signs of
– choledocholithiasis, pancreatic duct disruption
– impaired pancreatic perfusion
– di use or occasionally localized enlargement of pancreas due to in ammatory edema
– pancreatic- and/or peripancreatic-associated collections
– necrosis involving pancreas and/or peripancreatic tissues
● criteria for diagnosis of acute biliary pancreatitis (EASL Strong recommendation, Moderate-quality
evidence) (J Hepatol 2016 Jul;65(1):146 )
⚬ includes presence of
– upper abdominal pain
– gallbladder and/or common bile duct stones
– serum lipase and/or amylase > 3 times upper limit of normal
– altered liver function tests, such as elevations in bilirubin, aspartate aminotransferase (AST),
alanine aminotransferase (ALT), alkaline phosphatase, and gamma glutamyl-transpeptidase
● diagnosis of acute pancreatitis should be established within 48 hours of admission 3
● patients with acute cholangitis, jaundice, or acute pancreatitis should be evaluated for common bile
duct stones (EASL Strong recommendation, High-quality evidence) (J Hepatol 2016 Jul;65(1):146 )
Differential Diagnosis
● other causes of acute abdominal pain include
⚬ pneumonia
⚬ gallstones
⚬ appendicitis
⚬ aortic aneurysm
⚬ urinary calculus
⚬ penetrating peptic ulcer
⚬ gastric perforation
⚬ see Acute Abdominal Pain in Adults - Approach to the Patient for additional information
● other causes of elevated amylase and lipase 5
⚬ other pancreatic diseases
– pancreatic cancer
– pancreatic pseudocyst
– chronic pancreatitis
⚬ biliary tract disorders
– acute cholecystitis
– acute cholangitis
– choledocholithiasis
⚬ other gastrointestinal disorders
– intestinal obstruction, ischemia, or perforation

– peptic ulcer disease
– acute appendicitis
⚬ renal failure
● other causes of elevated amylase with normal lipase 5
⚬ salivary gland disorders (parotitis)

⚬ macroamylasaemia
⚬ decreased glomerular ltration (Lancet 2008 Jan 12;371(9607):143 )
⚬ neoplasm
– ovarian cancer and ovarian cysts (J Emerg Med 2010 May;38(4):463 )

– endometrioid adenocarcinoma (BMJ 2005 Oct 15;331(7521):890 )
– lung cancer
⚬ ectopic pregnancy
⚬ diabetic ketoacidosis
⚬ HIV infection
⚬ traumatic brain injury
⚬ Ebola virus infection (Dig Dis Sci 2015 Sep;60(9):2590 )
⚬ double balloon endoscopy (DBE) (post-DBE pancreatitis) (World J Gastroenterol 2010 May
21;16(19):2331 full-text )
⚬ multiple myeloma (Ann Clin Biochem 2002 Nov;39(Pt 6):616 )
⚬ bulimia (West J Med 1992 Dec;157(6):658 )
● other causes of increased serum lipase
⚬ mumps
⚬ types I and IV hyperlipidemias
⚬ gastrointestinal disease
– peptic ulcer disease (World J Gastroenterol 2017 Dec 28;23(48):8666 full-text )

– gastric perforation
⚬ in ammatory bowel disease
– celiac disease
– ulcerative colitis
⚬ hepatobiliary disease
– acute cholecystitis
– post cholecystectomy
– liver necrosis
⚬ acute renal failure

⚬ abdominal aortic aneurysm
⚬ trauma
– bone fracture
– crush injury
– fat embolism (Anaesthesia 2001 Feb;56(2):145 )
⚬ West Nile virus infection (N Engl J Med 2005 Jan 27;352(4):420 )
⚬ macrolipasemia, a rare cause of elevated serum lipase
⚬ Reference - HPB (Oxford) 2015 Feb;17(2):99 full-text
Testing Overview
● for diagnosis
⚬ blood testing for serum lipase and/or amylase levels
– in patients with abdominal pain that is consistent with acute pancreatitis, serum lipase and/or
amylase > 3 times upper limit of normal con rms the diagnosis of acute pancreatitis (ACG
Strong recommendation, Moderate-quality evidence)
– lipase testing is preferred over amylase in cases of suspected acute pancreatitis, due to
increased sensitivity of lipase testing
⚬ imaging with contrast-enhanced computed tomography (CECT) and/or magnetic resonance
imaging (MRI) recommended only if uncertain diagnosis or failure to improve clinically within 48-72
hours (ACG Strong recommendation, Low-quality evidence)
● to determine etiology
⚬ abdominal ultrasound recommended in all patients with acute pancreatitis to assess for gallstones
(ACG Strong recommendation, Low-quality evidence)
⚬ serum triglyceride level, if no gallstones or signi cant alcohol use (ACG Conditional
recommendation, Moderate-quality evidence)
⚬ endoscopic investigation for elusive etiologies should be limited in patients with acute pancreatitis,
risks and bene ts of such investigation unclear (ACG Conditional recommendation, Low-quality
evidence) 1 )
⚬ consider endoscopic ultrasound (EUS), or magnetic resonance cholangiopancreatography (MRCP),
if choledocholithiasis is highly suspected in the absence of cholangitis and/or jaundice (ACG
Conditional recommendation, Moderate-quality evidence)
⚬ for suspected atypical causes
– in patients > 40 years old, consider pancreatic tumor as a possible cause of acute pancreatitis
(ACG Conditional recommendation, Low-quality evidence) 1 )

– refer patients with recurrent idiopathic acute pancreatitis to expert centers (ACG Conditional
recommendation, Low-quality evidence) 1 )

– consider genetic testing in patients < 30 years old if no evident cause and family history of
pancreatic disease (ACG Conditional recommendation, Low-quality evidence) 1 )
● to assess severity and complications
⚬ tests for severity include blood urea nitrogen (BUN) and hematocrit, and C-reactive protein (CRP)
levels
⚬ additional blood tests for organ function/potential organ failure, such as albumin, glucose, liver
function tests, lactate dehydrogenase (LDH), white blood cell count, calcium, and arterial blood
gases can assess comorbidities and may inform prognostic scoring systems
⚬ consider CT-guided ne-needle aspiration for Gram stain and culture if suspected infected
necrosis, or empiric antibiotics (ACG Strong recommendation, Moderate-quality evidence)
⚬ perform endoscopic retrograde cholangiopancreatography (ERCP) within 24 hours if concurrent
acute cholangitis (ACG Strong recommendation, Moderate-quality evidence) but ERCP not needed
if no evidence of ongoing biliary obstruction (ACG Strong recommendation, Moderate-quality
evidence)
● other tests
⚬ rapid urinary trypsinogen-2 levels by dipstick testing may di erentiate acute pancreatitis from
other acute abdominal disease DynaMed Level 2 and cited by Japanese guidelines as potential
equivalent to elevated levels of pancreatic enzymes in the blood as criteria for diagnosis
⚬ abdominal x-ray may show associated ileus and chest x-ray may reveal pulmonary in ltrate or
e usion
Blood Tests
Pancreatic-specific Tests
CLINICIANS' PRACTICE POINT
Serum lipase levels tend to rise earlier and stay elevated longer in patients with acute
pancreatitis. Serum amylase levels may be normal in patients with ares of chronic pancreatitis
from conditions such as alcohol induced pancreatitis. Serum amylase testing should not be
considered as an initial laboratory test but reserved for situations when the diagnosis is in
question.
● lipase
⚬ serum lipase levels alone cannot be used to reliably diagnose acute pancreatitis, but may be used
to establish diagnosis if > 3 times upper limit of normal in presence of either 1 )

– abdominal pain consistent with disease, or
– characteristic ndings on abdominal imaging
⚬ serum lipase concentrations remain elevated longer than do serum amylase concentrations 1
– lipase has improved sensitivity, particularly in alcohol-induced pancreatitis, than amylase

– lipase levels peak at 24 hours but stay elevated for 8-14 days, therefore more useful when
patients may present > 24 hours after symptoms start
– Reference - Choosing Wisely American Society for Clinical Pathology 2019 Sep
⚬ lipase level unrelated to disease severity 3
STUDY
⚬ SUMMARY
serum lipase levels > 3 times upper limit of normal on admission may have moderate
sensitivity and specificity for diagnosing acute pancreatitis in patients presenting to
emergency department with acute abdominal pain DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2017 Apr 21;(4):CD012010 | Full Text
Details
– based on Cochrane review limited by heterogeneity
– systematic review of 10 diagnostic studies evaluating levels of serum amylase, serum lipase,
urinary trypsinogen-2, or urinary amylase for diagnosing acute pancreatitis in 5,056 patients
presenting to emergency department with acute abdominal pain
– 5 studies evaluated serum lipase levels > 3 times upper limit of normal on admission
– reference standard was consensus criteria or ndings by radiology or surgery
– median prevalence of acute pancreatitis 22.6% by reference standard
– all results for sensitivity and speci city limited by heterogeneity
– pooled performance of serum lipase levels > 3 times upper limit of normal on admission in
analysis of 4 studies with 678 patients
● sensitivity 79% (95% CI 54%-92%)
● speci city 89% (95% CI 46%-99%)
● positive predictive value 68.1% (95% CI 21.4%-94.3%)
● negative predictive value 6.6% (95% CI 2.7%-15.1%)
– Reference - Cochrane Database Syst Rev 2017 Apr 21;(4):CD012010 full-text
STUDY
⚬ SUMMARY
elevated lipase on day 1 may have better diagnostic accuracy compared to amylase variations
for diagnosis of acute pancreatitis DynaMed Level 2
DIAGNOSTIC COHORT STUDY: ANZ J Surg 2001 Oct;71(10):577

DIAGNOSTIC CASE-CONTROL STUDY: Am J Gastroenterol 1993 Dec;88(12):2051
Details
– based on diagnostic cohort study without independent validation and diagnostic case-control
study
– 328 patients with suspected pancreatitis (as indicated by laboratory request for serum amylase
estimation) had pancreatic enzyme levels evaluated
● reference standard was pancreatitis de ned by presence of clinical, laboratory, radiological,
or anatomic features
● 51 patients (5.5%) had acute pancreatitis
● for diagnosis of acute pancreatitis on day 1 of presentation
⚬ lipase > 208 units/L had 67% sensitivity and 97% speci city
⚬ serum total amylase > 176 units/L had 45% sensitivity and 97% speci city
● Reference - ANZ J Surg 2001 Oct;71(10):577
– 95 patients with nonpancreatic abdominal pain and 75 patients with acute pancreatitis
(diagnosis con rmed with imaging in 57 patients and made on clinical grounds in 18 patients)
had serum lipase and amylase levels compared
● for diagnosis of acute pancreatitis
⚬ lipase > 3 times normal had 100% sensitivity and 99% speci city
⚬ amylase ≥ 3 times normal had 72% sensitivity and 99% sensitivity
● Reference - Am J Gastroenterol 1993 Dec;88(12):2051
● amylase
⚬ American Society for Clinical Pathology recommends against testing for amylase in cases of
suspected acute pancreatitis, instead, test for lipase (Choosing Wisely 2016 Sept 16)
⚬ serum amylase levels alone cannot be used to reliably diagnose acute pancreatitis, but may be
used to establish diagnosis if > 3 times upper limit of normal in presence of either 1 , 2 , 3
– abdominal pain consistent with disease, or
– characteristic ndings on abdominal imaging
⚬ levels generally rise within a few hours after onset of symptoms and return to normal values within
3-5 days 1 )
⚬ amylase level unrelated to disease severity 3
⚬ levels may be normal in 1 )
– about 20% of patients at admission

– patients with alcohol induced acute pancreatitis
– patients with hypertriglyceridemia
– acute or chronic pancreatitis
⚬ elevated amylase levels may also be seen in patients with decreased glomerular ltration rates,
macroamylasemia, or several abdominal diseases such as acute appendicitis, peptic ulcer, or
intestinal obstruction 1
STUDY
⚬ SUMMARY
serum amylase levels > 3 times upper limit of normal on admission may have moderate
sensitivity but high specificity for diagnosing acute pancreatitis in patients presenting to
emergency department with acute abdominal pain DynaMed Level 2
Details
– 4 studies evaluated serum amylase levels > 3 times upper limit of normal on admission
– reference standard was consensus de nition of acute pancreatitis or radiological ndings
– all results for sensitivity and speci city limited by signi cant heterogeneity
– pooled performance of serum amylase levels > 3 times upper limit of normal on admission in
● sensitivity 72% (95% CI 59%-82%)
● speci city 93% (95% CI 66%-99%)
● positive predictive value 74% (95% CI 33.4%-94.1%)
● in patients diagnosed with acute pancreatitis, measurement of other enzymes not considered useful
for determining severity or outcome include
⚬ pancreatic isoamylase
⚬ elastase (also elevated in pancreatic cancer)
⚬ immunoreactive trypsinogen
⚬ Reference - Am J Gastroenterol 2002 Jun;97(6):1309
Differentiating Alcoholic from Biliary Pancreatitis
STUDY
● SUMMARY
alanine aminotransferase (ALT) ≥ 150 units/L may suggest gallstone pancreatitis as cause in
patients with acute pancreatitis DynaMed Level 2
SYSTEMATIC REVIEW: Am J Gastroenterol 1994 Oct;89(10):1863
Details
⚬ based on systematic review and meta-analysis without assessment of study quality
⚬ systematic review evaluating ALT, aspartate transaminase (AST),alkaline phosphatase, and bilirubin
testing for distinguishing gallstone pancreatitis in 8 diagnostic cohort studies including 557 patients
with acute pancreatitis
– ALT in 7 studies with 445 patients
– AST in 3 studies with 157 patients
– alkaline phosphatase in 4 studies with 322 patients
– bilirubin in 4 studies with 322 patients
⚬ ALT was the most clinically useful parameter

⚬ reference standards were sonography, computed tomographic scanning, endoscopic retrograde
cholangiopancreatography, or laparotomy
⚬ pooled prevalence for gallstone pancreatitis 52% in studies evaluating ALT
⚬ for diagnosis of gallstone pancreatitis, pooled diagnostic performance of ALT ≥ 150 units/L (about ≥
3-fold increase from baseline) had 48% sensitivity, 96% speci city and 95% positive predictive value
⚬ Reference - Am J Gastroenterol 1994 Oct;89(10):1863
STUDY
● SUMMARY
scoring based on 3 independent factors (female sex, age > 58 years, and alanine
aminotransferase > 150 units/L) may differentiate biliary pancreatitis from nonbiliary
pancreatitis DynaMed Level 2
Aliment Pharmacol Ther 2005 Sep 1;22(5):423
Details
⚬ based on diagnostic derivation cohort study
⚬ 139 patients with rst episode of acute pancreatitis were evaluated with laboratory testing
⚬ routine ultrasonography performed within 6 hours of admission; endoscopic ultrasonography
(EUS) performed within 24 hours of admission
⚬ biochemical analyses of blood samples for liver and renal function tests, arterial blood gases,
calcium level and lipid pro les performed after admission
⚬ biliary-related cause in 107 patients (77%) and nonbiliary cause (alcohol, hyperlipidemia, cancer,
idiopathic) in 32 patients (23%) by EUS
⚬ comparing biliary pancreatitis cases vs. nonbiliary pancreatitis cases
– median age 69 years vs. 51.5 years (p < 0.001)

– female sex 58% vs. 31% (p = 0.011)
– median serum total bilirubin level 39 mcmol/L vs. 15 mcmol/L (p < 0.001)
– serum alanine aminotransferase 150 units/L vs. 25 (p < 0.001)
– severe attack Ranson score ≥ 3 in 51% vs. 19% (p = 0.001)
⚬ 3 variables identi ed as independent predictive factors for biliary cause of acute pancreatitis were
– female sex
– age > 58 years
– serum alanine aminotransferase > 150 units/L
⚬ each variable scored 0 or 1

⚬ for identifying biliary pancreatitis total score ≥ 1 had
– sensitivity 93%
– speci city 56%
– positive predictive value 88%
– negative predictive value 72%
⚬ Reference - Aliment Pharmacol Ther 2005 Sep 1;22(5):423
STUDY
● SUMMARY
independent factors of age > 50 years, female sex, and alanine aminotransferase level at
admission > 2 times upper limit of normal may identify biliary cases of acute pancreatitis from
nonbilary cases DynaMed Level 2
COHORT STUDY: Pancreatology 2005;5(4-5):450
Details
⚬ based on prospective cohort study without validation cohort
⚬ 213 patients (median age 56 years) with rst episode acute pancreatitis
⚬ all patients had transabdominal ultrasonography and abdominal spiral computed tomography (CT)
scan; if biliary lithiasis not found, patients had endoscopic ultrasound (EUS)
⚬ patients classi ed into ‘biliary pancreatitis’ group if gallbladder or common bile duct lithiasis and no
other obvious cause of pancreatitis; if no procedure including EUS showed biliary lithiasis, patients
classi ed into ‘nonbiliary pancreatitis’ group
⚬ diagnosis of cholelithiasis or choledocholithiasis using EUS alone in 15% of all patients with biliary
lithiasis
⚬ causes of acute pancreatitis were
– biliary (62%)
– nonbiliary (38%)
● alcoholic (25%)
● other (7%)
● idiopathic (7%)
⚬ for identifying biliary origin pancreatitis
– female sex
● sensitivity 60%
● speci city 82%
● positive predictive value 84%
● negative predictive value 56%
– age > 50 years
● sensitivity 73%
● speci city 65%
– alanine transaminase level > 2 times upper limit of normal
● sensitivity 74%
● speci city 84%
⚬ Reference - Pancreatology 2005;5(4-5):450
Serum Triglyceride Levels
● obtain serum triglyceride level if no gallstones and/or signi cant history of alcohol use (ACG

⚬ consider hypertriglyceridemia as etiology of acute pancreatitis if > 1,000 mg/dL (11.3 mmol/L)
⚬ primary and secondary hypertriglyceridemia account for only 1%-4% of cases of acute pancreatitis
Liver Function Tests in Gallstone Pancreatitis
● liver enzymes normal in 15%-20% of patients with gallstone-associated acute pancreatitis (Lancet
2008 Jan 12;371(9607):143 )
STUDY
● SUMMARY
normal bilirubin level after 2 days of hospitalization for gallstone pancreatitis suggests low risk
for common bile duct stones DynaMed Level 2
DIAGNOSTIC COHORT STUDY: Am J Gastroenterol 1998 Apr;93(4):527
Details
⚬ based on derivation cohort study
⚬ 100 patients with gallstone pancreatitis and elective endoscopic retrograde
cholangiopancreatography (ERCP) or intraoperative cholangiography were evaluated
⚬ 21 patients had common bile duct stones
⚬ serum total bilirubin > 1.35 mg/dL (23 mcmol/L) on second hospital day occurred in 48 patients,
and was best clinical predictor of common bile duct stones
– sensitivity 90%
– speci city 63%
– positive predictive value 40%
– negative predictive value 96%
⚬ Reference - Am J Gastroenterol 1998 Apr;93(4):527 , editorial can be found in Am J Gastroenterol

1998 Apr;93(4):493
Tests for Severity
● blood urea nitrogen (BUN), creatinine, liver function tests, albumin, glucose, lactate dehydrogenase
(LDH), white blood cell count, hematocrit, calcium, and arterial blood gases may identify related
comorbidities and complications, and inform prognostic scoring systems
● markers of severity other than C-reactive protein (CRP) and hematocrit are not commonly used in
clinical practice 1
● CRP
⚬ most predictive 48-72 hours after onset of disease 2 , 5
⚬ levels > 150 mg/L at 48 hours after onset of symptoms predicts higher severity of acute
pancreatitis 2 , 5
– 80% sensitivity
– 76% speci city
– 67% positive predictive value
– 86% negative predictive value
STUDY
⚬ SUMMARY
C-reactive protein (CRP) level > 150 mg/L appears to have moderate-to-high accuracy for
predicting severity of acute pancreatitis DynaMed Level 2
SYSTEMATIC REVIEW: Front Physiol 2019;10:1002 | Full Text
Details
– based on systematic review with results limited by heterogeneity
– systematic review of 30 cohort studies (17 prospective and 13 retrospective) with 5,988 patients
with acute pancreatitis comparing the accuracy of CT-based scoring systems and laboratory
testing for predicting severity and mortality
● area under the curve (AUC) for the prediction of severity in 19 studies
● AUC for prediction of mortality in 11 studies
– C-reactive protein (CRP) measured 24-72 hours after admission (most at 48 hours after
admission)
– in studies evaluating CRP, range of reported severe acute pancreatitis 10.2%-43%, and range of
reported mortality 2%-12.5%
– pooled AUC of CRP level > 150 mg/L for predicting
● severity in acute pancreatitis 0.73 (CI 0.64-0.83) in analysis of 6 studies with 869 patients, with
results limited by heterogeneity
● mortality in acute pancreatitis 0.73 (CI 0.66-0.81) in analysis of 2 studies with 363 patients
– CRP level > 150 mg/L for severity of acute pancreatitis had
● sensitivity 71% (95% CI 59%-81%)

● speci city 87% (95% CI 66%-96%)
– Reference - Front Physiol 2019;10:1002 full-text
● hematocrit
STUDY
⚬ SUMMARY
admission hematocrit ≥ 44% or rise in blood urea nitrogen (BUN) at 24 hours may have
moderate-to-low accuracy for predicting persistent organ failure or pancreatic necrosis in
COHORT STUDY: Am J Gastroenterol 2015 Dec;110(12):1707
Details
– based on posthoc analysis of prospective cohort study data
– 1,612 patients (median age 53 years) with acute pancreatitis from 3 independent prospective
cohorts with clinical data were used to compare the accuracy of measured blood urea nitrogen
(BUN), hematocrit, and creatinine for predicting persistent organ failure (severe acute
pancreatitis) and pancreatic necrosis
– persistent organ failure developed in 18.2%; pancreatic necrosis in 25.4%; death in 4.9%
– for predicting persistent organ failure
● admission hematocrit ≥ 44% had
⚬ sensitivity 59%
⚬ speci city 74%
⚬ positive predictive value 37%
⚬ negative predictive value 88%
● rise in BUN at 24 hours had
⚬ sensitivity 63%
⚬ speci city 79%
– for predicting pancreatic necrosis
● admission hematocrit ≥ 44% had
⚬ sensitivity 54%
⚬ speci city 77%
● rise in BUN at 24 hours had
⚬ sensitivity 57%
⚬ speci city 77%
– admission hematocrit ≥ 44% and rise in BUN at 24 hours each associated with increased
● persistent organ failure (odds ratio [OR] 3.54, 95% CI 2.12 -5.91 and OR 5.84, 95% CI 2.64-
12.93, respectively)
● pancreatic necrosis (OR 3.11, 95% CI 1.84-5.26 and OR 4.07, 95% CI 2.04-8.12, respectively)
– Reference - Am J Gastroenterol 2015 Dec;110(12):1707
STUDY
⚬ SUMMARY
hematocrit at admission appears to have limited accuracy for predicting severity of acute
COHORT STUDY: World J Gastroenterol 2005 Nov 28;11(44):7018 | Full Text
Details
– based on cohort study
– 336 patients with rst episode of acute pancreatitis were evaluated
– 78 (23%) had severe acute pancreatitis
– hematocrit level > 44% in males and > 40% in females had
● sensitivity 59%
● speci city 35%
– Reference - World J Gastroenterol 2005 Nov 28;11(44):7018 full-text
Urine Studies
● rapid dipstick measurement of urinary trypsinogen-2
⚬ urinary trypsinogen-2 can be measured qualitatively by rapid dipstick measurement (Actim

Pancreatitis [Medix Biochemica] test)
– trypsinogen activation is believed to be involved in autodigestion of the pancreas in acute
pancreatitis
– urinary trypsinogen-2 (an isoenzyme of trypsinogen) is elevated within hours of acute
pancreatitis and decreases within about 3 days
– urine dipstick measurement can provide rapid qualitative testing for trypsinogen
– a positive test on dipstick measurement is seen with urinary trypsinogen-2 levels of > 50 ng/mL
(50 mcg/L)
– Reference - World J Gastroenterol 2019 Jan 7;25(1):107 full-text and - Cochrane Database
Syst Rev 2017 Apr 21;(4):CD012010 full-text
⚬ Japanese guidelines 2015 for management of acute pancreatitis state that rapid urinary
trypsinogen-2 testing may be a minimally invasive method for rapid diagnosis of acute pancreatitis
when blood testing not available
– Japanese criteria for acute pancreatitis require > 2 of the following
● acute abdominal pain and tenderness in the upper abdomen

● elevated levels of pancreatic enzymes in the blood or urine
● abnormal ndings of acute pancreatitis detected by ultrasound, computed tomography (CT)
or magnetic resonance imaging (MRI)
– rapid urinary trypsinogen-2 testing may not be commercially available
– Reference - JSHBPS 2015 full-text
STUDY
⚬ SUMMARY
dipstick measurement of urinary trypsinogen-2 levels > 50 ng/mL (50 mcg/L) on admission
may have moderate sensitivity but high specificity for diagnosing acute pancreatitis in
patients presenting to emergency department with acute abdominal pain DynaMed Level 2
Details
– 5 studies evaluated urinary trypsinogen-2 (Actim Pancreatitis [Medix Biochemica] test) levels >
50 ng/mL (50 mcg/L) on admission
– reference standard was consensus criteria, radiological ndings, pain, or serum amylase levels
– all results for sensitivity and speci city limited by heterogeneity
– pooled performance of urinary trypsinogen-2 levels > 50 ng/mL (50 mcg/L) on admission in
● sensitivity 72% (95% CI 56%-84%)
● speci city 90% (95% CI 85%-93%)
● positive predictive value 67.2% (95% CI 57.3%-75.7%)
STUDY
⚬ SUMMARY
urinary trypsinogen-2 levels > 50 mcg/L may differentiate acute pancreatitis from other
acute abdominal disease DynaMed Level 2
SYSTEMATIC REVIEW: Hepatobiliary Pancreat Dis Int 2013 Aug;12(4):355
Details
– based on systematic review with heterogeneity
– systematic review of 18 studies evaluating urinary trypsinogen-2 for di erentiating acute
pancreatitis from other acute abdominal disease or for predicting post-endoscopic retrograde
cholangiopancreatography (ERCP) pancreatitis
– all but 1 study used diagnostic cuto of 50 mcg/L
– reference standards used not reported
– for diagnosis of acute pancreatitis
● 14 studies evaluated with 2,659 patients and 852 cases of acute pancreatitis (32%
prevalence)
● pooled sensitivity 80% (95% CI 77%-82%), results limited by high degree of heterogeneity
● pooled speci city 92% (95% CI 91%-94%), results limited by high degree of heterogeneity
● diagnostic accuracy of urinary trypsinogen-2 was comparable to serum amylase (10 studies)
and lower than serum lipase (9 studies)
– for diagnosis of post-ERCP pancreatitis
● 3 studies evaluated with 285 patients

● pooled sensitivity 86% (95% CI 67%-96%)
● pooled speci city 94% (95% CI 91%-97%)
– Reference - Hepatobiliary Pancreat Dis Int 2013 Aug;12(4):355 in DARE 2014 Oct 1
– consistent results (82% pooled sensitivity and 93.5% pooled speci city) reported in meta-
analysis of 13 studies evaluating rapid urinary trypsinogen-2 test for diagnosis of acute
pancreatitis (Clin Biochem 2012 Sep;45(13-14):1051 )
– urinary trypsinogen-2 test had 68.6% sensitivity in 156 patients with acute pancreatitis and
87.1% speci city in 256 patients with nonpancreatic abdominal pain in prospective study in 21
hospitals in Japan (Pancreas 2012 Aug;41(6):869 )
Imaging Studies
Imaging Options
Abdominal Ultrasound
● perform transabdominal ultrasound in all patients with acute pancreatitis (ACG Strong
recommendation, Low-quality evidence) 1
● main bene t is identi cation of gallstones or evaluation for choledocholithiasis 1 , 6
● limitations for prognostication 6
⚬ when overlying bowel gas present

⚬ gallstones in the distal bile duct
X-ray
● abdominal x-ray may show gas- lled duodenum (sentinel loop) of localized ileus in severe pancreatitis
● chest x-ray may detect
⚬ elevated hemidiaphragm
⚬ pulmonary complications (in ltrates or pleural e usion)
● evidence of pulmonary complications may peak in early phase of severe acute pancreatitis
⚬ on admission, radiological abnormalities found in 15% of patients

⚬ by day 5, new radiological abnormalities can be seen in additional 71% of patients
● Reference - Lancet 2008 Jan 12;371(9607):143
Contrast-enhanced Computed Tomography (CECT)
● patients without any signs of severe acute pancreatitis who rapidly improve clinically usually do not
need a CECT 2
● reserve CECT and/or magnetic resonance imaging (MRI) of the pancreas for patients with either (ACG
Strong recommendation, Low-quality evidence) 1

⚬ unclear diagnosis
⚬ no clinical improvement within rst 48-72 hours after hospital admission
● potential role of CT in acute pancreatitis 1
⚬ con rmation of diagnosis

⚬ exclusion of alternative diagnosis
⚬ determination of severity (may be more accurate after 48-72 hours [time to establish necrosis])
⚬ identi cation of complications
● International Association of Pancreatology (IAP) and American Pancreatic Association (APA) guidelines
on acute pancreatitis include
⚬ reserve initial CT assessment. optimally at least 72-96 hours after onset of symptoms, for patients
with (IAP/APA Grade 1C, Strong Agreement)
– unclear diagnosis
– need for con rmation of severity based on clinical predictors of severe acute pancreatitis
– failure to respond to conservative treatment or in setting of clinical deterioration
⚬ consider follow up CT or MRI for clinical improvement failure, clinical deterioration, or when
invasive intervention is considered (IAP/APA Grade 1C, Strong Agreement)
⚬ Reference - Pancreatology 2013 Jul;13(4 Suppl 2):e1 full-text
● American College of Radiology (ACR) Appropriateness Criteria for acute pancreatitis guidance on
computed tomography (CT) includes
⚬ CT of abdomen and pelvis with IV contrast usually appropriate (ACR Rating 7-9) if
– suspected acute pancreatitis and initial presentation with atypical signs and symptoms;
including equivocal amylase and lipase values (possibly confounded by acute kidney injury or
chronic kidney disease) and when diagnoses other than pancreatitis may be possible (such as
bowel perforation, bowel ischemia)
– acute pancreatitis > 48-72 hours after onset of symptoms who are critically ill, or have systemic
in ammatory response syndrome (SIRS), or severe clinical scores
– acute pancreatitis and continued SIRS, severe clinical scores, leukocytosis, fever, and > 7-21 days
after onset of symptoms
– known necrotizing pancreatitis with signi cant deterioration in clinical status, including abrupt
decrease in hemoglobin or hematocrit, hypotension, tachycardia, tachypnea, abrupt change in
fever curve, or increase in white blood cells
– known pancreatic or peripancreatic uid collections with continued abdominal pain, early
satiety, nausea, vomiting, or signs of infection at > 4 weeks after symptom onset
⚬ CT of abdomen and pelvis with IV contrast may be appropriate if suspected acute pancreatitis and
initial presentation with epigastric pain, increased amylase and lipase, and < 48-72 hours after
symptom onset (ACR Rating 4-6)
⚬ Reference - J Am Coll Radiol 2019 Nov;16(11S):S316
● for diagnosis of acute pancreatitis, CECT has 90% sensitivity and 90% speci city 1
● CT images in acute pancreatitis
IMAGE 1 OF 3
CT of acute pancreatitis
Coronal C+ portal venous phase. Acute pancreatitis
(coronal). Abnormality is centered around the pancreas
with a walled-o region of low density. Features here are of

walled-o pancreatic necrosis associated with acute
pancreatitis. Abbreviation: CT, computed tomography.
IMAGE 2 OF 3
CT of acute pancreatitis
Features here are of walled-o pancreatic necrosis

associated with acute pancreatitis. Abbreviation: CT,
computed tomography.
● CECT most widely available imaging modality for uid collection imaging 2
Magnetic Resonance Imaging (MRI)
● reserve CECT and/or MRI of the pancreas for patients with either (ACG Strong recommendation, Low-
quality evidence) 1
⚬ unclear diagnosis
⚬ no clinical improvement within rst 48-72 hours after hospital admission
● American College of Radiology (ACR) Appropriateness Criteria for acute pancreatitis guidance on
magnetic resonance imaging (MRI) includes
⚬ MRI of abdomen without and with IV contrast with MR cholangiopancreatography (MRCP) usually
appropriate (ACR Rating 7-9) if
– suspected acute pancreatitis and initial presentation with atypical signs and symptoms;
including equivocal amylase and lipase values (possibly confounded by acute kidney injury or
chronic kidney disease) and when diagnoses other than pancreatitis may be possible (such as
bowel perforation, bowel ischemia)
– acute pancreatitis > 48-72 hours after onset of symptoms who are critically ill, or have systemic
in ammatory response syndrome (SIRS), or severe clinical scores
– acute pancreatitis and continued SIRS, severe clinical scores, leukocytosis, fever, and > 7-21 days
after onset of symptoms
– known pancreatic or peripancreatic uid collections with continued abdominal pain, early
satiety, nausea, vomiting, or signs of infection at > 4 weeks after symptom onset
⚬ MRI of abdomen without and with IV contrast with MRCP may be appropriate (ACR Rating 4-6) if
– suspected acute pancreatitis and initial presentation with epigastric pain, increased amylase
and lipase, and < 48-72 hours after symptom onset
– known necrotizing pancreatitis with signi cant deterioration in clinical status, including abrupt
decrease in hemoglobin or hematocrit, hypotension, tachycardia, tachypnea, abrupt change in
fever curve, or increase in white blood cells
⚬ Reference - J Am Coll Radiol 2019 Nov;16(11S):S316
● MRI may be alternative to CT for initial staging of severity of acute pancreatitis
STUDY
⚬ SUMMARY
high interobserver agreement reported comparing CECT with either nonenhanced or
contrast-enhanced MR cholangiopancreatography DynaMed Level 2
COHORT STUDY: Radiology 1999 Jun;211(3):727
Details
– based on cohort study without independent validation
– 30 patients with acute pancreatitis had CECT and nonenhanced and contrast-enhanced MR
images evaluated and compared by 2 blinded reviewers for establishing severity index based on
the presence of peripancreatic uid collections and pancreatic necrosis
– comparing CECT with nonenhanced MR cholangiopancreatography, high correlation between
reviewers (Spearman rank correlation (r) = 0.82, weighted kappa 0.79)
– comparing contrast-enhanced CT with enhanced MR cholangiopancreatography, high
correlation between reviewers (r = 0.82, weighted kappa 0.79)
– Reference - Radiology 1999 Jun;211(3):727
STUDY
⚬ SUMMARY
nonenhanced magnetic resonance imaging may reliably stage severity of acute pancreatitis
DynaMed Level 2
COHORT STUDY: J Magn Reson Imaging 2007 Aug;26(2):331
Details
– based on prospective cohort study without independent validation
– 90 patients with acute pancreatitis had nonenhanced magnetic resonance imaging (NE-MRI) and
CECT scan for assessment of severity of acute pancreatitis
– reference standard for assessment of severity was CECT scan
– Balthazar scoring system used for severity assessment
● four patients (4%) assessed as grade III by CT

● 19 patients (21.1%) classi ed as grade III by MRI
– good correlation between CT severity index and MRI severity index scores (Spearman's rank
correlation 0.6)
– for detecting severe acute pancreatitis based on imaging criteria, NE-MRI had sensitivity 100%,
speci city 82.6%, positive predictive value 100%, and negative predictive value 21%
– Reference - J Magn Reson Imaging 2007 Aug;26(2):331
⚬
CLINICIANS' PRACTICE POINT
In patients failing to improve after 48-72 hours (for example, with persistent pain, fever,
nausea, unable to begin oral feeding), contrast-enhanced computerized tomography (CECT) is
the preferred and most readily available imaging modality to aid the diagnosis of pancreatic
necrosis and evaluate the presence and development of local complications in acute
pancreatitis. Magnetic resonance imaging (MRI), by employing magnetic resonance
cholangiopancreatography (MRCP), is an excellent noninvasive modality to help stage the
severity of in ammatory processes and detect pancreatic necrosis; however, due to cost and
availability is most helpful in patients with a contrast allergy and renal insu ciency.
Endoscopic Ultrasound
● endoscopic ultrasound (EUS), or magnetic resonance cholangiopancreatography (MRCP), suggested to

screen for choledocholithiasis if highly suspected, in the absence of cholangitis and/or jaundice (ACG
● International Association of Pancreatology (IAP) and American Pancreatic Association (APA) guidelines
on acute pancreatitis include
⚬ on admission, in initial workup for etiology perform right upper quadrant ultrasonography
(IAP/APA Grade 1B, Strong Agreement)
⚬ if suspected idiopathic acute pancreatitis, after negative routine work-up for biliary etiology,
consider endoscopic ultrasonography (EUS) as rst step to assess for occult microlithiasis,
neoplasms and chronic pancreatitis (IAP/APA Grade 2C, Weak Agreement)
⚬ if EUS is negative, consider (secretin-stimulated) MRCP as second step to identify rare morphologic
abnormalities and CT of abdomen (IAP/APA Grade 2C, Weak Agreement)
⚬ if etiology remains unidenti ed consider genetic counseling (not necessarily genetic testing)
(IAP/APA Grade 2C, Weak Agreement)
⚬ Reference - Pancreatology 2013 Jul;13(4 Suppl 2):e1
● EUS may be needed initially or after recurrent episode of idiopathic acute pancreatitis 1
● EUS most sensitive imaging study for visualization of bile duct 5
STUDY
● SUMMARY
endoscopic ultrasound (EUS) may have higher diagnostic accuracy for biliary disease compared
to magnetic resonance cholangiopancreatography (MRCP) in patients with idiopathic acute
pancreatitis after routine laboratory testing and conventional radiologic methods
DynaMed Level 2
SYSTEMATIC REVIEW: Gastrointest Endosc 2018 May;87(5):1180
Details
⚬ based on systematic review of diagnostic cohort studies with methodologic limitations
⚬ systematic review of 34 diagnostic cohort studies evaluating endoscopic ultrasound (EUS) and/or
magnetic resonance cholangiopancreatography (MRCP) for etiologic diagnosis accuracy in patients
with idiopathic acute pancreatitis (IAP)
– EUS evaluated in 31 studies with 2,331 patients
– MRCP evaluated in 10 studies with 335 patients (5 studies MRCP with 195 patients and 5 studies
with MRCP after secretin stimulation [S-MRCP] with 140 patients)
– combination EUS and MRCP evaluated in 7 studies with 249 patients
⚬ IAP de ned as acute pancreatitis with no identi able etiology by routine laboratory studies and
conventional radiologic methods (transabdominal ultrasound [US] and computed tomography [CT])
⚬ methodologic limitations included use of retrospective and prospective studies and clinical
heterogeneity in prior radiologic studies before EUS or MRCP
⚬ comparing EUS vs. MRCP in analysis of 7 trials with 239 patients (MRCP completed in only 238
patients)
– overall diagnostic yield of 64% vs. 34% in analysis of 7 trials with 239 patients (MRCP completed
in only 238 patients) (p < 0.001)
– diagnostic yield for detecting biliary disease, including cholelithiasis, choledocholithiasis,
microlithiasis, and biliary sludge of 33% vs. 7% in subgroup analysis for etiology
– no signi cant di erence in diagnostic yield for detecting pancreatic divisum in subgroup analysis
for etiology
⚬ in subgroup analysis for detecting pancreatic divisum in IAP, diagnostic yield of 12% with S-MRCP
vs. 2% with MRCP vs. 2% with EUS
⚬ Reference - Gastrointest Endosc 2018 May;87(5):1180
Endoscopic Retrograde Cholangiopancreatography (ERCP)
● ERCP most appropriately used in patients with recurrent or relapsing acute pancreatitis 5
● perform ERCP within 24 hours of admission for patients with acute pancreatitis and concurrent acute
cholangitis (ACG Strong recommendation, Moderate-quality evidence) 1
● ERCP can also cause acute pancreatitis
● if choledocholithiasis (common bile duct stone) suspected
⚬ American Gastroenterological Association (AGA) 2007 guidelines recommend performing ERCP

within 72 hours if high suspicion of persistent common bile duct stone (visible on noninvasive
imaging, persistently dilated common bile duct, or jaundice) 5
⚬ American College of Gastroenterology (ACG) 2013 guidelines recommend MRCP or endoscopic
ultrasound (EUS) rather than diagnostic ERCP to screen for choledocholithiasis in absence of
cholangitis or jaundice (ACG Conditional recommendation, Moderate-quality evidence) 1
● routine use of urgent ERCP in patients with acute biliary pancreatitis and no cholangitis suggested
against (ACG Conditional recommendation, Low-quality evidence) 4
● ERCP is not needed in most patients with gallstone pancreatitis who lack laboratory or clinical
evidence of ongoing biliary obstruction (ACG Strong recommendation, Moderate-quality evidence) 1
● for prevention of post-ERCP pancreatitis, consider
⚬ rectal nonsteroidal anti-in ammatory drugs (NSAIDs), such as postprocedure rectal indomethacin
(ACG Conditional recommendation, Moderate-quality evidence; DynaMed Level 1
⚬ octreotide DynaMed Level 1
⚬ nitroglycerin DynaMed Level 2
⚬ guidewire-assisted cannulation during ERCP DynaMed Level 2

⚬ pancreatic duct stent (ACG Conditional recommendation, Moderate-quality evidence)
Magnetic Resonance Cholangiopancreatography (MRCP)
● MRCP may be used to detect biliary obstruction if contraindications to ERCP 2
● MRCP or EUS suggested to screen for choledocholithiasis if highly suspected in the absence of
cholangitis and/or jaundice (ACG Conditional recommendation, Moderate-quality evidence) 1
STUDY
● SUMMARY
magnetic resonance cholangiopancreatography (MRCP) may have lower diagnostic accuracy for
biliary disease compared to endoscopic ultrasound (EUS) in patients with idiopathic acute
pancreatitis after routine laboratory testing and conventional radiologic methods, but similar
diagnostic accuracy for detecting pancreatic divisum DynaMed Level 2
SYSTEMATIC REVIEW: Gastrointest Endosc 2018 May;87(5):1180
Details
⚬ based on systematic review of diagnostic cohort studies with methodologic limitations
⚬ systematic review of 34 cohort studies evaluating endoscopic ultrasound (EUS) and/or magnetic
resonance cholangiopancreatography (MRCP) for etiologic diagnosis accuracy in patients with
idiopathic acute pancreatitis (IAP)
– EUS evaluated in 31 studies with 2,331 patients
– MRCP evaluated in 10 studies with 335 patients (5 studies MRCP with 195 patients and 5 studies
with MRCP after secretin stimulation [S-MRCP] with 140 patients)
– combination EUS and MRCP evaluated in 7 studies with 249 patients
⚬ IAP de ned as acute pancreatitis with no identi able etiology by routine laboratory studies and
conventional radiologic methods (transabdominal ultrasound [US] and computed tomography [CT])
⚬ methodologic limitations included use of retrospective and prospective studies and clinical
heterogeneity in prior radiologic studies before EUS or MRCP
⚬ comparing EUS vs. MRCP in analysis of 7 trials with 239 patients (MRCP completed in only 238
patients)
– overall diagnostic yield of 64% vs. 34% in analysis of 7 trials with 239 patients (MRCP completed
in only 238 patients) (p < 0.001)
– diagnostic yield for detecting biliary disease, including cholelithiasis, choledocholithiasis,
microlithiasis, and biliary sludge of 33% vs. 7% in subgroup analysis for etiology
– no signi cant di erence in diagnostic yield for detecting pancreatic divisum in subgroup analysis
for etiology
⚬ in subgroup analysis for detecting pancreatic divisum in IAP, diagnostic yield of 12% with S-MRCP
vs. 2% with MRCP vs. 2% with EUS
⚬ Reference - Gastrointest Endosc 2018 May;87(5):1180
STUDY
● SUMMARY
MRCP appears able to rule out common bile duct stones DynaMed Level 2
RANDOMIZED TRIAL: J Am Coll Surg 2005 Jun;200(6):869

COHORT STUDY: Am J Gastroenterol 2005 May;100(5):1051
COHORT STUDY: AJR Am J Roentgenol 2005 Jun;184(6):1854
Details
⚬ based on randomized trial and 2 prospective cohort studies
⚬ 63 patients with mild resolving gallstone pancreatitis were randomized to laparoscopic
cholecystectomy (LC) and intraoperative cholangiography (IOC) (34 patients) vs. preoperative MRCP
(patients with negative MRCP underwent LC and IOC and patients with positive MRCP had
preoperative ERCP followed by LC (29 patients)
– common bile duct stones in 4 patients in LC/IOC group and 4 patients in MRCP group
– for diagnosis of common bile duct stones, MRCP had 100% sensitivity, 91% speci city, 50%
positive predictive value and 100% negative predictive value
– Reference - J Am Coll Surg 2005 Jun;200(6):869
⚬ 32 South Korean patients with suspected biliary pancreatitis and who had MRCP reviewed
– reference standard was ERCP

– 20 patients (63%) had common bile duct stones
– for diagnosis of common bile ducts stones, MRCP had 80% sensitivity, 83% speci city, 89%
positive predictive value and 71% negative predictive value
– for choledocholithiasis, agreement between MRCP and ERCP was 90.6% (kappa = 0.808)
– Reference - Am J Gastroenterol 2005 May;100(5):1051
⚬ 57 South Korean patients with symptomatic gallstone disease (with or without pancreatitis)
– 12 had common bile duct stones

– MRCP had 83% sensitivity, 93% speci city, 77% positive predictive value and 95% negative
predictive value
– Reference - AJR Am J Roentgenol 2005 Jun;184(6):1854
Image-based Classification of Pancreatic Local Complications
● interstitial edematous pancreatitis (IEP) 2
● ⚬ de ned as acute inflammation of pancreatic parenchyma and peripancreatic tissues, but without
recognizable tissue necrosis
⚬ CECT criteria
– pancreatic parenchyma enhancement by intravenous contrast agent

– no findings of peripancreatic necrosis
⚬ acute peripancreatic fluid collection (APFC) may occur 2
– de ned as peripancreatic fluid associated with IEP with no associated peripancreatic necrosis
(applies only to areas of peripancreatic fluid seen < 4 weeks after onset of IEP and without
features of a pseudocyst)
– CECT criteria
● occurs in setting of IEP

● homogeneous collection with fluid density
● confined by normal peripancreatic fascial planes
● no definable encapsulation
● adjacent to pancreas (no intrapancreatic extension)
– usually resolves spontaneously without treatment

– pancreatic pseudocyst may develop as complication
– see Pancreatic Pseudocyst for additional information
● necrotizing pancreatitis 2
⚬ de ned as inflammation associated with pancreatic parenchymal and/or peripancreatic necrosis
⚬ CECT criteria
– lack of pancreatic parenchymal enhancement by intravenous contrast agent and/or

– presence of findings of peripancreatic necrosis
⚬ acute necrotic collection (ANC) may develop 2
– de ned as collection containing variable amounts of both fluid and necrosis associated with
necrotizing pancreatitis that may or may not be infected
– can involve pancreatic parenchyma and/or peripancreatic tissues
– may be associated with disruption of the main pancreatic duct within the zone of parenchymal
necrosis
– CECT criteria
● occurs only in setting of acute necrotizing pancreatitis

● heterogeneous and nonliquid density of varying degrees in di erent locations (some appear
homogeneous early in their course)
● no definable encapsulating wall
● intrapancreatic and/or extrapancreatic
– MRI, transcutaneous ultrasonography, or endoscopic ultrasonography may be helpful to

confirm presence of solid content in uid collection
⚬ walled-o necrosis (WON) 2
IMAGE 3 OF 3
Pancreatic necrosis
Computed tomography scan demonstrating walled-o

pancreatic necrosis (arrows) virtually replacing the entire
pancreatic body and tail.
– de ned as mature, encapsulated collection of pancreatic and/or peripancreatic necrosis that

has developed well defined inflammatory wall
– previously called
● organized pancreatic necrosis

● necroma
● pancreatic sequestration
● pseudocyst associated with necrosis
● subacute pancreatic necrosis
– usually occurs > 4 weeks after onset of necrotizing pancreatitis

– CECT criteria
● heterogeneous with liquid and nonliquid density with varying degrees of loculations (some
may appear homogeneous)
● well-defined wall (completely encapsulated)
● intrapancreatic and/or extrapancreatic
– may be infected
– may be multiple
– may be present at sites distant from the pancreas
– MRI, transcutaneous ultrasonography or endoscopic ultrasonography may be helpful to confirm
presence of solid content in uid collection
● concept of "pancreatic abscess" no longer used or recommended because thought to be very rare 2
Other Diagnostic Testing
CT-guided Fine-needle Aspiration
● American Gastroenterological Association (AGA) recommendations 5
⚬ suspect infected necrosis in patients with sterile pancreatic necrosis if persistent or worsening
symptoms or if evidence of infection, usually after 7-10 days of illness
⚬ if infection suspected, perform CT-guided ne-needle aspiration (CT-FNA) with culture and Gram
stain of sample to document infection
● American College of Gastroenterology (ACG) recommendations 1
⚬ for possible infected necrosis (patients with pancreatic or extrapancreatic necrosis who deteriorate
or fail to improve after 7-10 days of hospitalization), management strategies include either of (ACG
– initial CT-FNA for Gram stain and culture to guide use of appropriate antibiotics
– empiric use of antibiotics without CT-FNA
Detection of Ampullary Obstruction
STUDY
● SUMMARY
clinical monitoring and lab testing may reliably identify patients with acute gallstone
pancreatitis and ampullary obstruction DynaMed Level 2
COHORT STUDY: Am J Gastroenterol 2000 Jan;95(1):122
Details
⚬ 132 patients with suspected acute gallstone pancreatitis evaluated with clinical monitoring
⚬ diagnosis of acute gallstone pancreatitis con rmed by surgery, ampullary obstruction con rmed by
intraoperative cholangiography (IOC) or endoscopic retrograde cholangiopancreatography (ERCP)
⚬ clinical diagnosis of ampullary obstruction based on
– severity of abdominal pain checked every 4-6 hours

– presence of bile in gastric aspirate checked every 6 hours
– serum bilirubin levels checked every 6 hours
⚬ for diagnosis of ampullary obstruction, clinical diagnosis had sensitivity 100%, speci city 92%,
positive predictive value 61%, negative predictive value 100%.
⚬ Reference - Am J Gastroenterol 2000 Jan;95(1):122
Management
Management Overview
● admit to general medicine unit if acute, mild uncomplicated pancreatitis

● admit to intensive care unit or intermediary care setting if organ failure (ACG Strong recommendation,
Low-quality evidence)
● provide aggressive hydration (such as lactated Ringer's solution 250-500 mL/hour) (ACG Strong
recommendation, Moderate-quality evidence); adequate uid resuscitation should maintain urine
output ≥ 0.5 mL/kg/hour without renal failure
● enteral nutrition preferred over parenteral nutrition
⚬ in mild acute pancreatitis, oral feeding may be started immediately if patients are asymptomatic
with feed (ACG Conditional recommendation, Moderate-quality evidence)
– immediate oral feeding may shorten hospital stay without increase in abdominal pain
DynaMed Level 2
– oral refeeding associated with about 20% rate of pain relapse in patients with acute pancreatitis
DynaMed Level 2 , uncertain if pain relapse rate would be lower with jejunal feeding
⚬ in severe acute pancreatitis, enteral nutrition recommended (ACG Strong recommendation, High-
quality evidence) and may reduce mortality, hospital stay and rates of infectious complications
compared to parenteral nutrition DynaMed Level 2
● analgesia important but insu cient evidence to suggest optimal drug selection
● role of antibiotics
⚬ give antibiotics for extrapancreatic infection, such as cholangitis, catheter-acquired infections,

bacteremia, urinary tract infections and/or pneumonia (ACG Strong recommendation, Moderate-
quality evidence)
⚬ prophylactic antibiotics not recommended in patients with severe acute pancreatitis, including
patients with sterile necrosis (ACG Strong recommendation, Moderate-quality evidence; IDSA
Grade A-I)
⚬ prophylactic antibiotics may not reduce mortality DynaMed Level 2
⚬ suspected infected necrosis,
– consider suspected infected necrosis in patients with pancreatic or extrapancreatic necrosis

who deteriorate or are not improving 7-10 days of hospitalization
– options for management include initial CT-guided ne needle aspiration (FNA) for Gram stain
and culture to guide use of appropriate antibiotics or empiric use of antibiotics without CT-
guided FNA (ACG Strong recommendation, Low-quality evidence)
– empiric antibiotic regimen options may include 14 days of
● imipenem-cilastatin 500 mg IV every 8 hours

● meropenem 1 g IV every 8 hours
● cipro oxacin 400 mg IV every 12 hours plus metronidazole 500 mg IV every 8 hours
● other medications with possible bene t
⚬ protease inhibitors may reduce mortality in patients with moderate-to-severe acute pancreatitis
DynaMed Level 2
⚬ somatostatin or octreotide may reduce mortality in patients with acute severe pancreatitis
DynaMed Level 2
● early endoscopic retrograde cholangiopancreatography (ERCP)
⚬ may reduce mortality and complication rate in patients with acute gallstone pancreatitis and
coexisting cholangitis or biliary obstruction DynaMed Level 2
⚬ may not reduce mortality or complication rate in acute gallstone pancreatitis (mild or severe)
without cholangitis or biliary obstruction DynaMed Level 2
● drainage or debridement
⚬ not recommended for asymptomatic pancreatic pseudocysts or necrosis (regardless of size or

location) (ACG Moderate recommendation, High-quality evidence)
⚬ delaying necrosectomy until 30 days after initial hospital admission associated with lower mortality
than earlier surgery in patients with necrotizing pancreatitis DynaMed Level 2
⚬ in symptomatic patients with infected necrosis, minimally invasive methods of necrosectomy are
preferred to open necrosectomy (ACG Strong recommendation, Low-quality evidence)
⚬ endoscopic and surgical step-up approaches associated with similar risk of major complications or
death DynaMed Level 2 but endoscopic approach reduces risk of pancreatic stula and length of
hospital stay DynaMed Level 1 in adults with infected necrotizing pancreatitis
● cholecystectomy recommended for gallstone pancreatitis
⚬ before discharge (optimally within 48 hours) in mild cases

⚬ after active in ammation and uid collections resolve or stabilize (> 2 weeks) in severe cases (ACG
Moderate recommendation, Moderate-quality evidence , DynaMed Level 2
● treatments reported to be e ective in hypertriglyceridemic pancreatitis include IV heparin, insulin,

brates, and plasmapheresis DynaMed Level 3
Treatment Setting
● most episodes of acute pancreatitis are mild (absence of organ failure and/or local complications),
needing only brief hospitalization 1
● perform risk assessment to di erentiate patients into higher- and lower-risk groups to determine
appropriate treatment setting, such as admission to general medicine or intensive care unit (ACG
Conditional recommendation, Low to moderate-quality evidence) 1
● consider intermediate care unit (stepdown unit) for patients at high risk of deterioration, such as
⚬ elderly patients
⚬ obese patients
⚬ patients needing large volume of resuscitation
⚬ patients with pancreatic necrosis
⚬ Reference - Lancet 2008 Jan 12;371(9607):143 , commentary can be found in Lancet 2008 Mar
29;371(9618):1072
● intensive care unit
⚬ admit patients with organ failure to intensive care unit or intermediary care setting whenever
possible (ACG Strong recommendation, Low-quality evidence) 1

⚬ admission to intensive care also indicated if severe disease, including presence of 1 , 3 , 6
– hypoxia
– tachypnea
– delirium
– signi cant gastrointestinal bleeding
– features of massive third-space loss (hypotension, tachycardia, azotemia, signi cant
hemoconcentration)
– evidence of persistent systemic in ammatory response syndrome (SIRS)
Fluid and Electrolytes
⚬ assess hemodynamic status immediately upon presentation and begin resuscitative measures as
needed (ACG Strong recommendation, Moderate-quality evidence)
⚬ provide aggressive hydration (250-500 mL/hour) to all patients in rst 12-24 hours unless
cardiovascular and/or renal comorbidities exist (ACG Strong recommendation, Moderate-quality
evidence)
⚬ more rapid repletion (bolus uids) may be needed in patients with severe volume depletion
(symptoms include hypotension and tachycardia) (ACG Strong recommendation, Moderate-quality
evidence)
⚬ lactated Ringer's solution may be preferential isotonic crystalloid replacement uid (ACG
⚬ reassess uid requirements at frequent intervals within 6 hours of admission and for the next 24-
48 hours to achieve decrease in blood urea nitrogen (ACG Strong recommendation, Moderate-
quality evidence)
● American Gastroenterological Association (AGA) recommends 4
⚬ goal-directed therapy for uid management, with no recommendation on whether normal saline
or Ringer's lactate be used (AGA Conditional recommendation, Very low-quality evidence)
⚬ against use of hydroxyethyl starch (HES) uids (AGA Conditional recommendation, Very low-quality
evidence)
● adequate uid resuscitation should maintain urine output ≥ 0.5 mL/kg/hour without renal failure 5
⚬ caution to avoid electrolyte disturbances and uid overload

⚬ uid de cits ≥ 5 L/day may occur
● crystalloid preferred in most instances over colloid 5
● use of colloid preferred in special circumstances 5
⚬ give packed red blood cells if hematocrit < 25%

⚬ give albumin if serum albumin level drops to 2 g/dL
STUDY
● SUMMARY
aggressive IV hydration may increase clinical improvement at 36 hours compared to standard
hydration in adults with mild acute pancreatitis DynaMed Level 2
RANDOMIZED TRIAL: Am J Gastroenterol 2017 May;112(5):797
Details
⚬ based on randomized trial with allocation concealment not stated
⚬ 60 adults (mean age 44 years) with mild acute pancreatitis without systemic in ammatory response
syndrome (SIRS) or organ failure were randomized to aggressive hydration (20 mL/kg bolus
followed by 3 mL/kg/hour infusion) vs. standard hydration (10 mL/kg bolus followed by 1.5
mg/kg/hour infusion) with Lactated Ringer solution
⚬ all patients had complete blood count, blood urea nitrogen (BUN), electrolytes, and creatinine
assessed at 12, 24, and 36 hours
⚬ primary outcome was clinical improvement at 36 hours, de ned as composite of decrease in BUN,
hematocrit, and creatinine, improvement in epigastric pain (using visual analog scale), and
tolerance of oral nutrition
⚬ comparing aggressive vs. standard hydration
– clinical improvement at 36 hours in 70% vs. 42% (p = 0.03)

– development of hemoconcentration in 11.1% vs. 36.4% (p = 0.003)
– development of SIRS in 14.8% vs. 27.3% (not signi cant)
– persistent SIRS in 7.4% vs. 21.2% (not signi cant)
⚬ Reference - Am J Gastroenterol 2017 May;112(5):797
STUDY
● SUMMARY
lactated Ringer's solution may reduce systemic inflammatory response syndrome (SIRS)
compared to normal saline in patients with acute pancreatitis DynaMed Level 3
RANDOMIZED TRIAL: Clin Gastroenterol Hepatol 2011 Aug;9(8):710
Details
⚬ based on small randomized trial without clinical outcomes
⚬ 40 patients with acute pancreatitis were randomized to 1 of 4 groups and followed for 24 hours
– goal-directed uid resuscitation with lactated Ringer's solution vs. normal saline
– standard uid resuscitation with lactated Ringer's solution vs. normal saline
⚬ comparing lactated Ringer's solution vs. normal saline, reduction in systemic in ammatory
response syndrome in 84% vs. 0% (p = 0.035, NNT 2)
⚬ no signi cant di erences between goal-directed vs. standard resuscitation in
– systemic in ammatory response syndrome

– C-reactive protein levels
– mean uid volume administered
⚬ Reference - Clin Gastroenterol Hepatol 2011 Aug;9(8):710
Diet
Recommendations for Nutrition Support
⚬ in patients with mild acute pancreatitis
– oral feedings may be started immediately if (ACG Conditional recommendation, Moderate-

quality evidence)
● no nausea or vomiting
● abdominal pain resolved
– initiation of feeding with low-fat solid diet appears as safe as clear liquid diet in patients (ACG
⚬ in patients with severe acute pancreatitis, use enteral nutrition rather than parenteral nutrition for
prevention of infectious complications; avoid parenteral nutrition unless the enteral route is not
available, not tolerated, or not meeting caloric requirements (ACG Strong recommendation, High-
quality evidence)
⚬ nasogastric and nasojejunal delivery of enteral feeding appear to be equally e ective and safe
(ACG Strong recommendation, Moderate-quality evidence)
⚬ early (within 24 hours) oral feeding as tolerated (AGA Strong recommendation, Moderate-quality
evidence)
⚬ enteral rather than parenteral nutrition recommended in patients with inability to feed orally (AGA
⚬ either nasogastric or nasoenteral route delivery of enteral tube feeding in patients with predicted
severe or necrotizing pancreatitis (AGA Conditional recommendation, Low-quality evidence)
⚬ enteral feeding initiated early in patients with pancreatic necrosis to decrease risk of infected
necrosis (Gastroenterology 2020 Jan;158(1):67 )
Enteral Nutrition Support
● previous strategy of avoiding oral feeding and keeping pancreas at "rest" not currently supported 1
● immediate oral refeeding appears safe in patients with mild acute pancreatitis 1
STUDY
⚬ SUMMARY
immediate oral feeding may shorten hospital stay without increase in abdominal pain in
patients with mild acute pancreatitis DynaMed Level 2
RANDOMIZED TRIAL: Clin Nutr 2007 Dec;26(6):758
Details
– based on randomized trial without blinding of assessors
– 60 patients with acute pancreatitis randomized to immediate oral feeding vs. fasting
– all patients had APACHE score < 8 and C-reactive protein (CRP) < 150 mg/L
– comparing immediate oral feeding vs. fasting
● mean length of hospital stay 4 vs. 6 days (p < 0.05)

● no signi cant di erence in abdominal pain or gastrointestinal symptoms
– Reference - Clin Nutr 2007 Dec;26(6):758
STUDY
⚬ SUMMARY
oral refeeding associated with about 20% rate of pain relapse in patients with acute
pancreatitis DynaMed Level 2 , uncertain if pain relapse rate would be lower with jejunal
feeding
SYSTEMATIC REVIEW: Am J Gastroenterol 2007 Sep;102(9):2079
Details
– based on systematic review of mostly observational data
– systematic review of 1 randomized trial of 28 patients and 2 nonrandomized studies of 246
patients with acute pancreatitis
– 21.9% had pain relapse during course of disease
– 17.1% had pain relapse within 48 hours after oral refeeding was started
– in randomized trial with 28 patients, pain relapse in none of jejunal feeding group vs. 14% of
oral feeding group (p = 0.06, not signi cant)
– Reference - Am J Gastroenterol 2007 Sep;102(9):2079
● dietetic formulation
STUDY
⚬ SUMMARY
insufficient evidence to select optimal formula for enteral nutrition in patients with acute
pancreatitis
SYSTEMATIC REVIEW: Br J Surg 2009 Nov;96(11):1243
Details
– based on systematic review of trials with methodologic limitations
– systematic review of 20 randomized trials evaluating di erent feeding formulas in 1,070 patients
– all trials had ≥ 1 methodological limitation including
● 13 trials without blinding

● 11 trials with unclear allocation concealment
● 11 trials with unclear sequence generation
– no signi cant di erence in feeding intolerance with
● (semi)elemental formulation vs. polymeric formulation

● supplementation of enteral nutrition with probiotics
● immunonutrition
– no signi cant di erence in risk of infectious complications or mortality in any comparison

– Reference - Br J Surg 2009 Nov;96(11):1243
STUDY
⚬ SUMMARY
initiating oral nutrition with low-fat solid diet after mild acute pancreatitis may not change
length of hospital stay DynaMed Level 2
RANDOMIZED TRIAL: Clin Gastroenterol Hepatol 2007 Aug;5(8):946
Details
– based on randomized trial without blinding
– 121 patients with mild acute pancreatitis were randomized to low-fat solid diet (LFSD) vs. clear
liquid diet (CLD) and followed for 28 days after refeeding initiated
– no signi cant di erence in length of hospitalization between groups
– Reference - Clin Gastroenterol Hepatol 2007 Aug;5(8):946 full-text
STUDY
⚬ SUMMARY
initial oral feeding with soft diet appears to decrease hospital stay compared with clear liquid
diet in patients with mild acute pancreatitis DynaMed Level 2
RANDOMIZED TRIAL: Aliment Pharmacol Ther 2008 Sep 15;28(6):777
Details
– based on randomized trial without blinding of outcome assessors
– 101 patients with acute mild pancreatitis were randomized to clear liquid diet vs. soft diet as
initial oral feeding and followed to discharge
– comparing soft diet vs. clear liquid diet median length of hospitalization
● postrefeeding 4 vs. 6 days (p < 0.0001)

● total 5 vs. 8 days (p < 0.0001)
– Reference - Aliment Pharmacol Ther 2008 Sep 15;28(6):777
STUDY
⚬ SUMMARY
dietetic formulation of initial meal may not affect clinical outcomes for patients with mild
acute pancreatitis DynaMed Level 2
RANDOMIZED TRIAL: J Clin Gastroenterol 2010 Aug;44(7):517
Details
– based on randomized trial without intention-to-treat analysis
– 221 patients with mild acute pancreatitis were randomized to 1 of 3 groups and followed to 7
days after discharge
● clear liquid diet, with low proportion of fat and with gradual increase in amounts of solid
calories, proteins, and fat during subsequent days
● soft diet, with average proportion of fat and with gradual increase in the amounts of solid
calories during the subsequent days
● full solid diet, with normal amounts of calories and fat throughout the refeeding period
– 210 patients analyzed

– no signi cant di erences during oral refeeding between diet groups for
● pain relapse
● length of hospital stay
– Reference - J Clin Gastroenterol 2010 Aug;44(7):517
STUDY
● SUMMARY
enteral immunonutrition may reduce all-cause mortality in adults with acute pancreatitis
DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2015 Mar 23;(3):CD010605
Details
⚬ based on Cochrane review of trials with methodologic limitations
⚬ systematic review of 15 randomized trials evaluating enteral nutrition in 1,376 adults with acute
pancreatitis
⚬ all but 1 trial had ≥ 1 limitation including
– unclear allocation concealment

– unclear or no blinding
⚬ immunonutrition de ned as enteral nutrition supplemented with substances potentially able to

change the immune response
⚬ comparing enteral immunonutrition to no enteral immunonutrition
– enteral immunonutrition associated with decreased all-cause mortality in analysis of 6 trials with
520 adults
● risk ratio (RR) 0.49 (95% CI 0.29-0.8)
● NNT 9-32 with 16% mortality in no enteral immunonutrition group
– no signi cant di erences in systemic in ammatory response syndrome (SIRS), organ failure,
local septic complications, length of hospital stay, and adverse events
⚬ comparing ber-enriched enteral nutrition to no ber-enriched enteral nutrition
– organ failure in 85.7% with ber-enriched enteral nutrition vs. 100% with no ber-enriched
enteral nutrition (p = 0.04, NNT 7) in 1 trial with 60 adults
– ber-enriched enteral nutrition associated with decreased length of hospital stay (mean
di erence -9.28 days, -13.21 to -5.35 days) in analysis of 2 trials with 103 adults
– no signi cant di erences in all-cause mortality, SIRS, and local septic complications
⚬ comparing probiotics to no probiotics
– probiotics associated with nonsigni cant reduction in local septic complication (RR 0.69, 95% CI
0.46-1.05) in analysis of 6 trials with 666 patients
– no signi cant di erences in all-cause mortality, SIRS, organ failure, length of hospital stay, and
adverse events (results for all-cause mortality and organ failure limited by signi cant
heterogeneity)
⚬ mean length of hospital stay 15.8 days with immunonutrition plus probiotics plus ber vs. 21 days
with conventional treatment (p = 0.01) in 1 trial with 64 adults
⚬ Reference - Cochrane Database Syst Rev 2015 Mar 23;(3):CD010605
● see Enteral Nutrition Support in Adults for additional information
Early vs. Late Nutritional Intervention
STUDY
● SUMMARY
early enteral nutrition may decrease infectious complications and mortality compared to late
enteral nutrition or total parental nutrition in patients with acute pancreatitis DynaMed Level 2
SYSTEMATIC REVIEW: PLoS One 2013;8(6):e64926 | Full Text
Details
⚬ based on systematic review of studies with methodologic limitations
⚬ systematic review of 11 studies (9 randomized trials and 2 retrospective observational studies)
comparing enteral nutrition within 48 hours vs. total parenteral nutrition or late enteral nutrition
(control) in 775 patients with acute pancreatitis
⚬ nasojejunal feeding in 9 studies and nasogastric feeding in 2 studies
⚬ all studies had ≥ 1 limitation including
– unclear or inadequate methods randomization

– unclear or inadequate allocation concealment
– lack of blinding of patients, caregivers, and outcome assessors
⚬ comparing early enteral nutrition to control (late enteral nutrition or total parenteral nutrition),
enteral nutrition associated with reduced
– overall infectious complications in analysis of 10 studies with 732 patients
● odds ratio (OR) 0.38 (95% CI 0.21-0.68)

● NNT 4-12 with 38% risk of infection in control group
● with results limited by heterogeneity
– catheter-related septic complications in analysis of 6 studies with 261 patients
● OR 0.26 (95% CI 0.11-0.58)

● NNT 6-14 with 20% risk of catheter-related septic complications in control group
– pancreatic infectious complications in analysis of 7 studies with 609 patients
● OR 0.49 (95% CI 0.31-0.78)

● NNT 10-33 with 16% risk of pancreatic infection complications in control group
– mortality in analysis of 6 studies with 313 patients
● OR 0.31 (95% CI 0.14-0.71)

● NNT 9-28 with 14% mortality in control group
– length of hospital stay (mean di erence -2.18 days, 95% CI -3.48 to -0.87 days) in analysis of 3
studies with 104 patients
– organ failure in analysis of 6 studies with 256 patients
● OR 0.27 (95% CI 0.14-0.5)

● NNT 4-7 with 38% risk of organ failure in control group
⚬ no signi cant di erences between groups in pulmonary complications in analysis of 8 trials

⚬ in analysis of subgroups strati ed to severe acute pancreatitis (SAP), predicted severe acute
pancreatitis (pSAP), or mild AP (MAP)
– in patients with SAP or pSAP comparing early enteral nutrition in patients to control (late enteral
nutrition or total parenteral nutrition), enteral nutrition associated with reduced
● overall infectious complications in analysis of 7 studies with 573 patients (OR 0.34, 95% CI
0.15-0.77), with results limited by heterogeneity
● catheter-related septic complications in analysis of 5 studies with 229 patients (OR 0.27, 95%
CI 0.11-0.62)
● pancreatic infection complications in analysis of 5 studies with 480 patients (OR 0.53, 95% CI
0.31-0.89)
– in patients with MAP comparing early enteral nutrition in patients to control, no signi cant
di erences in overall infectious complications or catheter-related septic complications in 1 study
with 32 patients with MAP
⚬ Reference - PLoS One 2013;8(6):e64926 full-text
STUDY
● SUMMARY
early feeding does not appear to increase length of hospital stay compared to delayed feeding in
patients with acute pancreatitis and might reduce stay in patients with mild-to-moderate
disease DynaMed Level 2
SYSTEMATIC REVIEW: Ann Intern Med 2017 Jun 20;166(12):883
Details
⚬ based on systematic review limited by clinical heterogeneity
⚬ systematic review of 11 randomized trials comparing early vs. delayed feeding (≤ 48 vs. > 48 hours
after hospitalization) in adults hospitalized with acute pancreatitis
⚬ routes of feeding included oral, nasogastric, nasojejunal, and nasoenteric with intermittent
parenteral feeding permitted in 1 trial and total parenteral feeding permitted in 3 trials as
physician's discretion
⚬ criteria for feeding initiation in early and delayed groups varied across trials
⚬ meta-analysis not performed because of heterogeneity of feeding protocols and reported
outcomes
⚬ length of hospital stay reported in 7 trials with patients with mild-to-moderate pancreatitis, and 3
with patients with predicted severe pancreatitis
⚬ for length of hospital stay
– in patients with mild-to-moderate pancreatitis
● early feeding associated with decrease in length of hospital stay in 4 trials with 270 patients
● no signi cant di erence in 3 trials with 211 patients
– in patients with predicted severe pancreatitis
● no signi cant di erences in 2 trials with 419 patients

● early feeding associated with decrease in length of hospital stay in 1 trial with 43 patients
⚬ in patients with mild-to-moderate pancreatitis
– no deaths reported in 5 trials with 407 patients

– no signi cant di erence in rehospitalization in 2 trials with 94 patients
⚬ other outcomes had variable reporting and heterogeneous results

⚬ no trial showed signi cant increase in adverse events or worsening of symptoms with early
feeding, regardless of severity of pancreatitis
⚬ Reference - Ann Intern Med 2017 Jun 20;166(12):883
STUDY
● SUMMARY
early enteral feeding does not appear to decrease risk of major infection or death compared to
delayed oral diet with enteral feeding if needed in adults with acute pancreatitis at high risk of
complications DynaMed Level 2
RANDOMIZED TRIAL: N Engl J Med 2014 Nov 20;371(21):1983
Details
⚬ based on randomized trial with wide con dence intervals
⚬ 208 adults presenting to emergency department with rst episode of acute pancreatitis were
randomized to 1 of 2 nutritional interventions and followed for 6 months
– early enteral feeding by nasoenteric tube initiated within 24 hours
– oral diet initiated at 72 hours with nasoenteric tube feeding provided if the oral diet was not
tolerated
⚬ all patients had high risk of complications (de ned as Acute Physiology and Chronic Health
Evaluation II score ≥ 8, Imrie or modi ed Glasgow score ≥ 3, or serum C-reactive protein level > 150
mg/L)
⚬ 69% in oral diet group did not require tube feeding
⚬ major infection was composite of infected pancreatic necrosis, bacteremia, and pneumonia
⚬ comparing early enteral feeding vs. oral diet
– major infection in 25% vs. 26% (risk ratio [RR] 0.97, 95% CI 0.7-1.34)
– death in 11% vs. 7% (RR 1.27, 95% CI 0.85-1.89)
– necrotizing pancreatitis in 63% vs. 62% (not signi cant)
⚬ no signi cant di erences in rates of admission to intensive care unit, mechanical ventilation, or
new-onset organ failure
⚬ Reference - PYTHON trial (N Engl J Med 2014 Nov 20;371(21):1983 , commentary can be found in
Gastroenterology 2015 Jun;148(7):1476 )
STUDY
● SUMMARY
early nasogastric feeding and early nasojejunal feeding may have similar clinical outcomes in
patients with severe acute pancreatitis DynaMed Level 2
RANDOMIZED TRIAL: Am J Gastroenterol 2005 Feb;100(2):432
Details
⚬ based on small randomized trial
⚬ 50 adults with severe acute pancreatitis randomized to nasogastric feeding vs. nasojejunal feeding
⚬ no signi cant di erences between groups in
– pain
– duration of hospital stay
– mortality
⚬ Reference - Am J Gastroenterol 2005 Feb;100(2):432
Enteral vs. Parenteral Nutrition
● enteral nutrition support may result in fewer infectious complications, lower mortality, and shorter
hospital stay compared to parenteral nutrition support in patients with acute pancreatitis
STUDY
⚬ SUMMARY
enteral nutrition appears more effective than parenteral nutrition in patients with acute
COCHRANE REVIEW: Cochrane Database Syst Rev 2010 Jan 20;(1):CD002837
Details
– based on Cochrane review of trials without blinding
– systematic review of 8 randomized trials comparing total parenteral nutrition vs. enteral
nutrition in 348 patients with acute pancreatitis
– enteral nutrition associated with reduction in
● mortality in analysis of all trials (relative risk [RR] 0.5, 95% CI 0.28-0.91, NNT 9-70 assuming
16% mortality in parenteral group)
⚬ larger bene t reported in analysis of 4 trials with 136 patients with severe pancreatitis
⚬ RR 0.18 (95% CI 0.06-0.58), NNT 5-10 assuming mortality in 24% of parenteral group
● multiple organ failure in analysis of 6 trials with 278 patients (RR 0.55, 95% CI 0.37-0.81)
● systemic infection in analysis of 7 trials with 259 patients (RR 0.39, 95% CI 0.23-0.65)
● operative interventions in analysis of 7 trials with 316 patients (RR 0.44, 95% CI 0.29-0.67)
● mean length of hospital stay (-2.37 days, 95% CI -7.18 to 2.44 days, not signi cant) in analysis
of 4 trials with 145 patients
– Reference - Cochrane Database Syst Rev 2010 Jan 20;(1):CD002837 , commentary can be
found in Ann Intern Med 2010 Jul 20;153(2):JC1
STUDY
⚬ SUMMARY
enteral nutrition may reduce infectious complications compared to parenteral nutrition in
SYSTEMATIC REVIEW: Aliment Pharmacol Ther 2008 Sep 15;28(6):704
Details
– based on systematic review with trials without blinding
– systematic review of 15 randomized trials evaluating enteral or parenteral nutrition in 593
– comparing enteral vs. parenteral nutrition
● infectious complications in 16.2% vs. 39.4% in meta-analysis of 10 trials with 430 patients (p <
0.0001, NNT 5)
● mortality in 8.4% vs. 16% in meta-analysis of 9 trials with 404 patients (not signi cant)
– comparing parenteral nutrition vs. no supplemental nutrition
● infectious complications in 16.3% vs. 16.3% in 2 trials with 98 patients (not signi cant)
● mortality in 7.1% vs. 22.8% in 3 trials with 113 patients (p = 0.04, NNT 7)
– comparing enteral nutrition vs. no supplemental nutrition
● ndings reached by indirect comparison

● reduced mortality
● di erence in infectious complications not signi cant due to wide con dence intervals
– Reference - Aliment Pharmacol Ther 2008 Sep 15;28(6):704 , commentary can be found in ACP
J Club 2008 Dec 16;149(6):6
STUDY
⚬ SUMMARY
enteral nutrition may reduce mortality and rates of infectious complications and pancreatic
infection compared to parenteral nutrition in patients with severe acute pancreatitis
DynaMed Level 2
SYSTEMATIC REVIEW: Arch Surg 2008 Nov;143(11):1111
Details
– based on systematic review of moderate-quality trials
– systematic review of 5 randomized trials comparing enteral and parenteral nutrition in 202
patients with severe acute pancreatitis
– comparing enteral vs. parenteral nutrition
● mortality 4% vs. 15.9% (relative risk [RR] 0.32, p = 0.03, NNT 9) in meta-analysis of 4 trials with
183 patients
● any infectious complication in 22.1% vs. 43% (RR 0.47, p < 0.001, NNT 5) in meta-analysis of 5
trials
● pancreatic infection in 11.6% vs. 22.4% (RR 0.48, p = 0.02, NNT 10) in meta-analysis of 5 trials
– no signi cant di erence between groups in rates of organ failure

– Reference - Arch Surg 2008 Nov;143(11):1111
STUDY
⚬ SUMMARY
enteral nutrition associated with reduced infectious morbidity and hospital length of stay
compared to parenteral nutrition in patients with acute pancreatitis DynaMed Level 2
SYSTEMATIC REVIEW: JPEN J Parenter Enteral Nutr 2006 Mar-Apr;30(2):143
Details
– based on systematic review with trial-speci c quality measures not reported
– systemic review of 27 randomized controlled trials comparing enteral vs. parenteral nutrition in
– in analysis of 7 trials comparing enteral vs. parenteral nutrition support, enteral nutrition
support associated with
● reduction in infectious morbidity (risk ratio 0.46, p = 0.001)
● hospital length of stay (weighted mean di erence -3.94 days, p < 0.0001)
● reduced organ failure (risk ratio 0.59, p = 0.18)
● no e ect on mortality
– individual studies re ect enteral nutrition support associated with
● reduction in oxidative stress

● faster resolution of disease
● lower cost
– Reference - JPEN J Parenter Enteral Nutr 2006 Mar-Apr;30(2):143 , commentary can be found
in JPEN J Parenter Enteral Nutr 2006 Nov-Dec;30(6):536
STUDY
⚬ SUMMARY
enteral nutrition via nasojejunal tube associated with fewer septic complications and shorter
hospital stay compared to parenteral nutrition in patients with acute pancreatitis
DynaMed Level 2
RANDOMIZED TRIAL: BMJ 2004 Jun 12;328(7453):1407 | Full Text
Details
– based on systematic review of small randomized trials without blinding
– systematic review of 6 randomized trials comparing enteral vs. parenteral nutrition in 263
– all trials used nasojejunal tube for enteral nutrition
– quality of randomization varied and no studies were blinded
– comparing enteral nutrition vs. parenteral nutrition
● septic complications in 10.4% vs. 28.3% (p = 0.004, NNT 6)

● shorter hospital stay (mean 1.6 days vs. 4.3 days, p < 0.001)
● surgical interventions to control pancreatitis in 8.9% vs. 10.6% (p = 0.05, NNT 59)
● mortality 7.2% vs. 11.6% (not signi cant)
● noninfectious complications in 17.4% vs. 30.3% (not signi cant)
– Reference - BMJ 2004 Jun 12;328(7453):1407 full-text , commentary can be found in

Gastroenterology 2005 Mar;128(3):798
● see also
⚬ Parenteral Nutrition Support in Adults

⚬ Parenteral Nutrition Support Complications
Medications
Pain Relief
● parenteral narcotics often used for pain relief 5
STUDY
● SUMMARY
opioids that may reduce need for supplementary analgesia in patients with acute pancreatitis
pain include pentazocine and buprenorphine DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2013 Jul 26;(7):CD009179
Details
⚬ systematic review of 5 randomized trials evaluating opioids in 227 patients with acute pancreatitis
pain
⚬ all trials had ≥ 1 limitation including
– unclear allocation concealment

– lack of blinding
– small sample size
⚬ signi cantly decreased need for supplementary analgesia with
– pentazocine vs. procaine in 1 trial with 107 patients

– buprenorphine vs. procaine in 1 trial with 39 patients
⚬ no signi cant di erence in pain intensity or need for supplementary analgesia comparing
– morphine vs. metamizole in 1 trial with 16 patients

– buprenorphine vs. pethidine (meperidine) in 1 trial with 32 patients
⚬ Reference - Cochrane Database Syst Rev 2013 Jul 26;(7):CD009179
STUDY
● SUMMARY
no clinical evidence to favor meperidine over morphine for pain control in patients with acute
pancreatitis
LITERATURE REVIEW: Am J Gastroenterol 2001 Apr;96(4):1266
Details
⚬ based on literature review
⚬ meperidine traditionally advised because of concern regarding morphine causing spasm of
sphincter of Oddi and increased biliary pressure
⚬ all narcotics, including morphine and meperidine, increase biliary pressure and decrease sphincter
of Oddi peristalsis
⚬ no studies identi ed comparing di erent narcotics with regard to clinical outcomes
⚬ additional considerations
– morphine associated with longer pain relief

– meperidine may cause seizures
⚬ Reference - Am J Gastroenterol 2001 Apr;96(4):1266
STUDY
● SUMMARY
pentazocine may reduce pain and increase pain-free periods more than diclofenac in patients
with mild acute pancreatitis DynaMed Level 2
RANDOMIZED TRIAL: Am J Gastroenterol 2019 May;114(5):813
Details
⚬ based on small randomized trial
⚬ 50 patients (mean age 38 years) hospitalized with mild acute pancreatitis (≤ 7 days onset of pain)
randomized to pentazocine 30 mg IV vs. diclofenac 75 mg IV every 8 hours for 24 hours and
followed to 40 hours (8 hours after last dose)
⚬ rescue analgesic was fentanyl 0.3 mcg/kg on demand with 15 minute lockout interval and 1 hour
limit of 1.2 mcg/kg
⚬ pain relief measured by dose of rescue analgesic fentanyl needed
⚬ 1 patient in diclofenac group crossed over to pentazocine group at 24 hours; study medication
stopped in 2 patients due to disease-related multiorgan failure
⚬ comparing pentazocine vs. diclofenac
– median total rescue analgesic fentanyl needed of 126 mcg vs. 226 mcg (p = 0.028)
– pain-free period (without rescue analgesia) of 31 hours vs. 28 hours (p = 0.047)
– no signi cant di erence in median number of rescue analgesic demands
⚬ study medication-related adverse events were nausea and vomiting requiring antiemetics in 1
patient with pentazocine vs. 3 patients with diclofenac
⚬ Reference - Am J Gastroenterol 2019 May;114(5):813
STUDY
● SUMMARY
increased opioid use for acute pain in adults hospitalized with acute pancreatitis may be
associated with longer length of hospital stay and increased risk of persistent opioid use after
discharge compared to no opioid use DynaMed Level 2
COHORT STUDY: JAMA Netw Open 2019 Apr 5;2(4):e191827 | Full Text
Details
⚬ 4,307 adults (median age 57 years) hospitalized with acute pancreatitis evaluated for association
between opioid-based analgesic use and hospital stay or persistent opioid use after discharge
⚬ baseline opioid use determined as total IV morphine equivalent doses (MEDs) of narcotic analgesic
medication dispensed during rst 12 hours of hospitalization
⚬ persistent opioid use de ned as opioid dispensation at discharge or within rst 2 weeks after
discharge and again within 90 to 180 days from discharge
⚬ 3,443 adults (79.9%) received baseline opioids, and 388 adults (9.6%) had persistent opioid use
after discharge
– 2,354 patients (54.7%) had gallstone-related diseases
– 1,471 patients (34.2%) had a history of alcohol use
⚬ median length of stay of 5 days in adults receiving highest quintile of baseline MEDs vs. 3 days in
adults not receiving opioids (p < 0.001)
⚬ factors associated with increased risk of persistent opioid use
– every 1-unit increase of baseline MEDs (odds ratio 1.02, 95% CI 1-1.04)
– every 1-unit increase of average MED per day during entire hospital stay (odds ratio 1.02, 95% CI
1.01-1.03)
⚬ Reference - JAMA Netw Open 2019 Apr 5;2(4):e191827 full-text
Antibiotics
Prophylactic Antibiotics
⚬ routine use of prophylactic antibiotics is not recommended in patients with severe acute
pancreatitis (ACG Strong recommendation, Moderate-quality evidence)
⚬ use of prophylactic antibiotics in patients with sterile necrosis to prevent infected necrosis is not
recommended (ACG Strong recommendation, Moderate-quality evidence)
⚬ routine administration of prophylactic or therapeutic antifungal agents with antibiotics is not
recommended (ACG Conditional recommendation, Low-quality evidence)
● Infectious Disease Society of America (IDSA) and Surgical Infection Society recommends against
administering prophylactic antibiotics to patients with severe necrotizing pancreatitis prior to the
diagnosis of infection (IDSA Grade A-I) (Surg Infect (Larchmt) 2010 Feb;11(1):79 PDF )
● American Gastroenterological Association (AGA) recommends against use of prophylactic antibiotics

in patients with predicted severe acute pancreatitis and necrotizing pancreatitis (ACG Conditional
recommendation, Low-quality evidence) 4
● prophylactic antibiotics may reduce bacteremia but do not appear to reduce mortality in patients
having ERCP DynaMed Level 2
STUDY
● SUMMARY
antibiotics may not reduce short-term mortality in patients with acute pancreatitis
DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2017 Apr 21;(4):CD011384
Details
⚬ based on Cochrane review with con dence intervals that cannot exclude di erences that may be
clinically important
⚬ systematic review of 84 randomized trials evaluating pharmacologic interventions in 8,234 patients
⚬ comparing antibiotics to control, no signi cant di erences in
– short-term mortality at up to 3 months (odds ratio 0.81, 95% CI 0.57-1.15) in analysis of 17 trials
with 1,058 patients
– serious adverse events at up to 3 months in analysis of 5 trials with 304 patients
– organ failure at up to 3 months in analysis of 5 trials with 258 patients
– infected pancreatic necrosis at up to 3 months in analysis of 11 trials with 714 patients
⚬ consistent results in subgroups of patients with acute necrotizing pancreatitis and severe acute
pancreatitis
⚬ Reference - Cochrane Database Syst Rev 2017 Apr 21;(4):CD011384
STUDY
● SUMMARY
prophylactic antibiotics may not reduce mortality in patients with acute necrotizing pancreatitis
DynaMed Level 2
SYSTEMATIC REVIEW: Cochrane Database Syst Rev 2010 May 12;(5):CD002941

SYSTEMATIC REVIEW: Scand J Gastroenterol 2011 Mar;46(3):261
SYSTEMATIC REVIEW: World J Gastroenterol 2012 Jan 21;18(3):279
Details
⚬ based on 3 systematic reviews of trials with methodologic limitations
⚬ Cochrane review of 7 randomized trials evaluating antibiotics in 404 patients with acute
pancreatitis and pancreatic necrosis
● lack of blinding in 5 trials
● lack of or unclear allocation concealment in 3 trials
● unclear randomization in 6 trials
● inadequate statistical power in all trials
– overall, antibiotics associated with nonsigni cant reduction in
● mortality (risk ratio [RR] 0.6, 95% CI 0.34-1.05), no individual trial had signi cant mortality
reduction in analysis of 7 trials with 404 patients
● nonpancreatic infections (RR 0.62, 95% CI 0.36-1.06) in analysis of 5 trials with 318 patients
– no signi cant di erences overall comparing antibiotics versus placebo or no antibiotic in
● infected pancreatic necrosis

● fungal infection
● overall infection
● need for surgery
– no signi cant di erences reported in analyses limited to beta-lactam trials or quinolone trials
for any outcome
– compared with placebo or no antibiotic in analysis of 3 trials with 160 patients
● imipenem associated with reduction in infected pancreatic necrosis
⚬ RR 0.34 (95% CI 0.13-0.84)

⚬ NNT 5-26 with 24.4% infected pancreatic necrosis in placebo or no antibiotic group
● imipenem associated with reduced overall infection
⚬ RR 0.49 (95% CI 0.28-0.87)

⚬ NNT 3-5 with 52.4% rate of overall infection in placebo or no antibiotic group
● no signi cant di erences in need for surgery

● no signi cant di erences in need for surgery or mortality
– Reference - Cochrane Database Syst Rev 2010 May 12;(5):CD002941
–
DynaMed Commentary
In the trials included in this systematic review, most of the nonpancreatic infections
included hospital-acquired infections (such as pneumonia, urinary tract infection, and
catheter-associated infections), which may not be caused by pancreatitis and for which
prophylactic antibiotic use is not currently recommended.
⚬ systematic review of 14 randomized trials evaluating prophylactic antibiotics vs. placebo or no

antibiotic in 841 patients with acute pancreatitis
● lack of blinding in 11 trials

● lack of or unclear allocation concealment in 10 trials
● small size
● inadequate statistical power
– comparing prophylactic antibiotics to placebo or no antibiotic, no signi cant reduction in
● mortality in analysis of all 14 trials

● infected pancreatic necrosis in analysis of all 14 trials
● need for surgery in analysis of 13 trials with 815 patients
– comparing carbapenem-based therapy to placebo/no antibiotic in analysis of 8 trials with 514

patients, no signi cant reduction in
● mortality
● need for surgery
– Reference - Scand J Gastroenterol 2011 Mar;46(3):261
⚬ systematic review of 11 randomized trials (all included in above systematic review) evaluating
prophylactic antibiotic use vs. placebo or no antibiotics in 622 patients with severe pancreatitis
– funnel plot indicated possible publication bias in trials conducted before 2000
– compared with placebo or no antibiotic, prophylactic antibiotics associated with
● reduced mortality in analysis of 4 trials with 278 patients before 2000
⚬ risk ratio (RR) 0.31 (95% CI 0.12-0.79)

⚬ NNT 16-27 with 18.2% mortality in placebo group
● no signi cant di erence in mortality in analysis of 7 trials with 439 patients after 2000
– Reference - World J Gastroenterol 2012 Jan 21;18(3):279 full-text
Antibiotics for Infected Necrosis
⚬ for possible infected necrosis (patients with pancreatic or extrapancreatic necrosis who deteriorate
or fail to improve after 7-10 days of hospitalization), management strategies include either of (ACG
– initial computed tomography (CT)-guided ne-needle aspiration (FNA) for Gram stain and
culture to guide use of appropriate antibiotics
– empiric use of antibiotics without CT-FNA
⚬ for infected necrosis, consider broad-spectrum IV antibiotics known to penetrate pancreatic

necrosis (such as carbapenems, quinolones, and metronidazole) (ACG Conditional
recommendation, Moderate-quality evidence) 1
– to delay or avoid surgical intervention
– to decrease morbidity and mortality
● if used prior to con rmation of organism and sensitivity, choice of antibiotic includes
⚬ imipenem-cilastatin 500 mg IV every 8 hours for 14 days 5
⚬ meropenem 1 g IV every 8 hours for 14 days 5
⚬ alternative is cipro oxacin 400 mg IV every 12 hours plus metronidazole 500 mg IV every 8 hours
for 14 days (World J Emerg Surg 2006 Jul 4;1:20 full-text )
Antibiotics for Extrapancreatic Infections
● give antibiotics for extrapancreatic infection, including (ACG Strong recommendation, Moderate-
quality evidence) 1
⚬ cholangitis
⚬ catheter-acquired infections
⚬ bacteremia
⚬ urinary tract infections
⚬ pneumonia
Protease Inhibitors
STUDY
● SUMMARY
addition of nafamostat mesylate to imipenem may reduce mortality compared to IV imipenem
only in patients with severe acute pancreatitis DynaMed Level 2
RANDOMIZED TRIAL: Pancreas 2010 Aug;39(6):863
Details
⚬ based on randomized trial with di erential loss to follow-up
⚬ 78 patients with severe acute pancreatitis randomized to continuous regional arterial infusion
(CRAI) of nafamostat mesylate plus imipenem vs. IV imipenem only
– CRAI group received continuous infusion of nafamostat mesylate 240 mg/day plus imipenem 1
g/day intra-arterially (via one of the arteries perfusing the pancreas) for 5 days, followed by
imipenem 0.5 g IV every 8 hours for 9 days
– imipenem group received imipenem 0.5 g IV every 8 hours for 14 days
⚬ study completion rates were 79% for CRAI vs. 100% for imipenem
⚬ comparing CRAI vs. imipenem
– mortality 5.1% vs. 23.1% (p = 0.02, NNT 6)

– patients requiring urgent surgery 10.3% vs. 33.3% (p = 0.01, NNT 5)
⚬ Reference - Pancreas 2010 Aug;39(6):863
STUDY
● SUMMARY
gabexate and aprotinin each may not reduce short-term mortality in patients with acute
Details
⚬ based on Cochrane review with con dence interval that cannot exclude di erences that may be
⚬ systematic review of 84 randomized trials evaluating pharmacologic interventions in 8,234 patients
⚬ comparing aprotinin (an anti brinolytic molecule) to control, no signi cant di erences in
– short-term mortality at up to 3 months in analysis of 7 trials with 651 patients

– sepsis at up to 3 months in analysis of 2 trials with 103 patients
⚬ comparing gabexate (a serine protease inhibitor) to control, no signi cant di erences in
– short-term mortality at up to 3 months (odds ratio 0.79, 95% CI 0.48-1.3) in analysis of 5 trials
with 576 patients
– organ failure at up to 3 months in 1 trial with 50 patients
– sepsis at up to 3 months in analysis of 3 trials with 373 patients
⚬ Reference - Cochrane Database Syst Rev 2017 Apr 21;(4):CD011384
Insulin
● insulin (often temporarily) needed in 5
⚬ most patients with severe acute pancreatitis

⚬ many patients with milder disease
Probiotics and Selective Decontamination
EVIDENCE SYNOPSIS
Enterally fed probiotics may not be e ective treatment or reduce either mortality or infectious
complications in patients with severe acute pancreatitis.
STUDY
⚬ SUMMARY
probiotics do not appear effective in patients with predicted severe acute pancreatitis
DynaMed Level 2
SYSTEMATIC REVIEW: Crit Care 2014 Mar 31;18(2):R57 | Full Text
Details
– based on systematic review limited by clinical heterogeneity
– systematic review of 6 randomized trials comparing probiotics vs. placebo in 536 patients with
predicted severe acute pancreatitis
– trials were heterogeneous in probiotic type, dose, and duration of treatment
– comparing probiotics vs. placebo, no signi cant di erences in
● mortality in analysis of 5 trials

● infection of necrotic pancreas tissue in analysis of 5 trials
● total infection in analysis of 3 trials
● need for surgery in analysis of 4 trials
● length of hospital stay in analysis of 3 trials
– Reference - Crit Care 2014 Mar 31;18(2):R57 full-text
STUDY
⚬ SUMMARY
enterally fed probiotics not associated with reduced mortality or infection in patients with
severe acute pancreatitis DynaMed Level 2
SYSTEMATIC REVIEW: Langenbecks Arch Surg 2009 Jan;394(1):171
Details
– based on systematic review limited by heterogeneity
– systematic review of 4 randomized trials evaluating enteral feeding with probiotics vs. without
probiotics in 428 patients with severe acute pancreatitis (of alcoholic or biliary etiology)
– no signi cant di erences in
● infected pancreatic necrosis in analysis of 3 trials with 403 patients, results limited by
signi cant heterogeneity
● mortality in analysis of 3 trials with 403 patients, results limited by signi cant heterogeneity
● mean duration of hospital stay in analysis of 2 trials with 321 patients, results limited by
● requiring surgical operation in analysis of 3 trials with 403 patients, results limited by
– no signi cant di erence in other infectious complications including
● chest infection
● urinary tract infection
● systemic in ammatory response syndrome
– Reference - Langenbecks Arch Surg 2009 Jan;394(1):171
STUDY
⚬ SUMMARY
probiotic combination increases mortality and bowel ischemia in patients with predicted
RANDOMIZED TRIAL: Lancet 2008 Feb 23;371(9613):651
Details
– based on randomized trial
– 298 patients with predicted severe acute pancreatitis randomized to multispecies probiotic vs.
placebo (starting within 72 hours of symptom onset) twice daily enterally for 28 days
– 2 patients who did not have pancreatitis were not analyzed
– infectious complications de ned as any of (during admission and 90-day follow-up)

● bacteremia
● pneumonia
● urosepsis
● infected ascites
– comparing probiotic vs. placebo
● mortality in 16% vs. 6% (p = 0.01, NNH 10)

● bowel ischemia in 5.9% (9 patients) vs. 0 (p = 0.004, NNH 17) (8 of these 9 patients died)
● infectious complications in 30% vs. 28% (not signi cant)
– Reference - Lancet 2008 Feb 23;371(9613):651 , correction can be found in Lancet 2008 Apr
12;371(9620):1246, editorial can be found in Lancet 2008 Feb 23;371(9613):634 ,
commentary can be found in Lancet 2008 Jul 12;372(9633):112 , Lancet 2010 Mar
13;375(9718):875 (commentary can be found in Lancet 2010 Apr 10;375(9722):1249 )
● evidence con icting for e cacy of selective decontamination
STUDY
⚬ SUMMARY
selective decontamination of alimentary tract may reduce mortality and pancreatic infections
in patients with severe acute pancreatitis DynaMed Level 2
RANDOMIZED TRIAL: Ann Surg 1995 Jul;222(1):57 | Full Text
Details
– based on randomized trial with unclear randomization method
– 102 patients with severe acute pancreatitis randomized to selective decontamination vs.
standard treatment
– selective decontamination consisted of
● colistin 200 mg, amphotericin 500 mg and nor oxacin 50 mg orally every 6 hours
● similar drugs and doses by rectal enema daily
● 2% paste of same drugs applied to gums and tracheostomy (if present) every 6 hours
● cefotaxime 500 mg IV every 8 hours until gram-negatives eliminated from oral cavity and
rectum
– comparing selective decontamination vs. control
● mortality 22% vs. 35% (p = 0.048, NNT 8)

● pancreatic infection in 18% vs. 38% (p = 0.003, NNT 5)
● laparotomies performed per patient 0.9 vs. 3.1 (p < 0.05)
– Reference - Ann Surg 1995 Jul;222(1):57 full-text
STUDY
⚬ SUMMARY
selective decontamination of digestive tract may not be associated with significantly better
outcomes in patients with severe acute pancreatitis DynaMed Level 2
COHORT STUDY: J Hepatobiliary Pancreat Surg 2007;14(5):503
Details
– based on retrospective cohort study
– 90 patients with severe acute pancreatitis were divided into 3 groups based on whether they
had selective decontamination of digestive (SDD) tract with or without enteral nutrition (EN)
● no SDD, no EN (group A, 20 patients)
● SDD, no EN (group B, 32 patients)
● SD with EN (group C, 38 patients)
– SDD consisted of mixture of polymyxin B (500,000 units), L-glutamine (1 g), and lactulose (30 mL)
given 3 times daily for 7 days via tube in proximal jejunum
– comparing SDD vs. no SDD groups (group A vs. group B)
● organ dysfunction 59% vs. 70% (not signi cant)

● mortality 28% vs. 40% (not signi cant)
– Reference - J Hepatobiliary Pancreat Surg 2007;14(5):503 , editorial can be found in BMJ 2004
Apr 24;328(7446):968 , commentary can be found in BMJ 2004 Jul 24;329(7459):232
Other Medications
● octreotide (long-acting synthetic analogue of somatostatin) or somatostatin
STUDY
⚬ SUMMARY
octreotide may reduce serious adverse events and organ failure in patients with acute
Details
– based on Cochrane review of trials with methodologic limitations (for organ failure outcome)
and without signi cant di erence in high-quality trial (for serious adverse events outcome)
– systematic review of 84 randomized trials evaluating pharmacologic interventions in 8,234
– all trials comparing octreotide to control and reporting on organ failure outcome had ≥ 1
methodologic limitation(s) including small sample size or unclear allocation concealment
– comparing octreotide to control
● octreotide associated with
⚬ decrease in number of serious adverse events in analysis of 4 trials with 770 patients
– risk ratio 0.74 (95% CI 0.6-0.89)

– analysis included 1 high-quality trial with results nonsigni cantly favoring octreotide
⚬ decrease in organ failure (odds ratio 0.51, 95% CI 0.27-0.97) in analysis of 2 trials with 430
patients
● no signi cant di erences in
⚬ short-term mortality in analysis of 5 trials with 927 patients

⚬ sepsis in analysis of 2 trials with 340 patients
– Reference - Cochrane Database Syst Rev 2017 Apr 21;(4):CD011384
STUDY
⚬ SUMMARY
somatostatin may not reduce short-term mortality in patients with acute pancreatitis
DynaMed Level 2
Details
– based on Cochrane review with con dence interval that cannot exclude di erences that may be
– comparing somatostatin to control, no signi cant di erences in
● short-term mortality (odds ratio 0.57, 95% CI 0.29-1.1) in analysis of 6 trials with 493 patients
● number of serious adverse events in analysis of 3 trials with 257 patients
STUDY
⚬ SUMMARY
addition of crude rhubarb to somatostatin therapy may reduce risk of complications and
shorten duration of abdominal pain and hospitalization in patients with acute pancreatitis
DynaMed Level 2
SYSTEMATIC REVIEW: J Ethnopharmacol 2016 Dec 24;194:495
Details
– based on systematic review of trials with unclear blinding
– systematic review of 19 randomized trials evaluating addition of crude rhubarb to somatostatin
in 1,161 patients with acute pancreatitis
– crude rhubarb 10-90 g/day given by gastric tube or retention enema
– comparing crude rhubarb plus somatostatin to somatostatin alone
● crude rhubarb plus somatostatin associated with
⚬ reduced risk of complications (pancreatic necrosis, pseudocyst, pancreatic abscess

formation, sepsis, renal failure, or multiple organ dysfunction syndrome) (risk ratio 0.55,
95% CI 0.4-0.7) in analysis of 9 trials with 441 patients
⚬ shorter duration of abdominal pain (weighted mean di erence [WMD] -1.3 days, 95% CI
-1.6 to -1.1 days) in analysis of 14 trials with 910 patients, results limited by signi cant
heterogeneity
⚬ shorter duration of hospitalization (WMD -6.7 days, 95% CI -8.8 to -4.6 days) in analysis of
10 trials with 546 patients, results limited by signi cant heterogeneity
⚬ shorter time to rst defecation (WMD -2.3 days, 95% CI -3.1 to -1.5 days) in analysis of 9
trials with 614 patients, results limited by signi cant heterogeneity
⚬ reduced Acute Physiology and Chronic Health Evaluation II (APACHE II) scores (WMD 1.2,
95% CI 0.41-1.91) in analysis of 5 trials with 266 patients, results limited by signi cant
heterogeneity
● no signi cant di erence in mortality in analysis of 7 trials with 441 patients
– Reference - J Ethnopharmacol 2016 Dec 24;194:495
● lexipafant
⚬ antagonist of platelet activating factor (thought to be central to systemic in ammatory response
syndrome [SIRS]) 5
STUDY
⚬ SUMMARY
lexipafant might reduce short-term mortality in patients with acute pancreatitis
DynaMed Level 2
Details
– based on Cochrane review with con dence intervals that includes di erences that are not
– comparing lexipafant to control, lexipafant associated with
● nonsigni cant decrease in short-term mortality (odds ratio [OR] 0.55, 95% CI 0.3-1.01) in
analysis of 3 trials with 423 patients
● decrease in serious adverse events (number) (risk ratio 0.67, 95% CI 0.46-0.96) in 1 trial with
290 patients
● decrease in sepsis (OR 0.26, 95% CI 0.08-0.83) in 1 trial with 290 patients
– no signi cant di erence in organ failure in analysis of 2 trials with 340 patients
STUDY
● SUMMARY
Chinese medicinal herbs may improve clinical outcomes in patients with acute pancreatitis
DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2009 Jul 8;(3):CD003631
Details
⚬ based on Cochrane review of trials with methodological limitations
⚬ systematic review of 15 randomized trials evaluating Chinese medicinal herbs in 845 patients with
acute pancreatitis
⚬ all trials published in Chinese and all included inpatients
⚬ Chinese medicinal herb treatments included Chinese rhubarb and/or alone, or in
combination with herbal compounds
– Qingyitang
– Dacaihu Tang
– Huanglianjiedu Tang and Dachengqi Tang
– Dan-shen
– Qingganlidan Tang
– Danyi Tang
– Chaishaochengqi Tang
– Tongxiahuayu
⚬ methodological limitations included
– absent allocation concealment in all trials

– absent blinding in all trials
⚬ compared with usual care, addition of Chinese herbs associated with decrease in
– mortality (risk ratio [RR] 0.43, 95% CI 0.23-0.8) in analysis of 6 trials with 287 patients
– multiple organ failure (RR 0.51, 95% CI 0.27-0.96) in analysis of 2 trials with 85 patients
– systemic infection (RR 0.24, 95% CI 0.1-0.59) in analysis of 4 trials with 212 patients
⚬ Reference - Cochrane Database Syst Rev 2009 Jul 8;(3):CD003631
Surgery and Procedures
Endoscopic Retrograde Cholangiopancreatography (ERCP)
⚬ perform ERCP within 24 hours for patients with gallstone pancreatitis with cholangitis
⚬ perform ERCP within 72 hours if high suspicion of persistent common bile duct stone, such as
– visible common bile duct stone on noninvasive imaging

– persistently dilated common bile duct
– jaundice
⚬ endoscopic sphincterotomy in the absence of choledocholithiasis at time of procedure is

reasonable therapeutic option, but data supporting this practice are lacking
⚬ performance of ERCP within 24 hours for predicted or actual severe gallstone pancreatitis is
controversial in the absence of cholangitis or high suspicion of persistent common bile duct stone
⚬ if un t for surgery, ERCP and sphincterotomy provide adequate long-term therapy
STUDY
● SUMMARY
among patients with acute gallstone pancreatitis, early ERCP may reduce mortality and
complication rate in patients with coexisting cholangitis or biliary obstruction, but not in
patients without cholangitis or biliary obstruction DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2012 May 16;(5):CD009779
Details
⚬ systematic review of 7 randomized trials comparing early routine ERCP vs. early conservative
management (with or without selective ERCP) in 757 patients with suspected acute gallstone
pancreatitis
⚬ methodological limitations included
– unclear allocation concealment in 6 studies

– all but 1 trial with 103 patients had ≥ 1 methodological limitations
⚬ no signi cant di erences in overall analysis in
– mortality in analysis of 5 trials with 644 patients, results limited by signi cant heterogeneity
– local complications in analysis of 4 trials with 517 patients
– systemic complications in analysis of 4 trials with 406 patients
⚬ in subgroup analysis of patients with coexisting cholangitis or biliary obstruction, early ERCP
associated with
– decreased mortality in analysis of 5 trials with 416 patients
● risk ratio (RR) 0.2 (95% CI 0.06-0.68)

● NNT 16-45 with 7% mortality in early conservative management group
– decreased local complications in analysis of 3 trials with 236 patients
● RR 0.45 (95% CI 0.2-0.99)

● NNT 8-625 with local complications in 16% of early conservative management group
– decreased systemic complications in analysis of 4 trials with 363 patients
● RR 0.37 (95% CI 0.18-0.78)

● NNT 9-33 with systemic complications in 14% of early conservative management group
⚬ Reference - Cochrane Database Syst Rev 2012 May 16;(5):CD009779
STUDY
● SUMMARY
urgent ERCP with biliary sphincterotomy may not reduce mortality or major complications
compared to conservative treatment in adults with predicted severe gallstone pancreatitis
without cholangitis DynaMed Level 2
RANDOMIZED TRIAL: Lancet 2020 Jul 18;396(10245):167
Details
⚬ based on randomized trial with wide con dence interval
⚬ 232 adults (mean age 70 years) with predicted severe gallstone pancreatitis without cholangitis
were randomized to urgent ERCP with biliary sphincterotomy vs. conservative treatment and
followed for 6 months
– urgent ERCP was performed ≤ 24 hours after admission to emergency department and ≤ 72
hours after symptom onset
– patients in conservative treatment group received supportive treatment, with on-demand ERCP
with biliary sphincterotomy performed in those who developed cholangitis; elective ERCP was
done in cases of persistent cholestasis or retained bile duct stones following recovery from
initial pancreatitis episode
⚬ all patients had Acute Physiology and Chronic Health Evaluation (APACHE-II) score ≥ 8 points, Imrie
or modi ed Glasgow score ≥ 3 points, or serum C-reactive protein > 150 mg/L within 24 hours of
admission
⚬ main exclusion criteria were cholangitis, pancreatitis due to other causes, previous sphincterotomy
or needle knife precut, and history of chronic pancreatitis
⚬ primary outcome was composite of mortality and major complications, de ned as new-onset
persistent organ failure, pancreatic parenchymal necrosis, bacteremia, cholangitis, pneumonia, or
pancreatic endocrine or exocrine insu ciency
⚬ ERCP performed in 96% of urgent ERCP group and in 31% of conservative treatment group
⚬ 99% included in analysis
⚬ comparing urgent ERCP vs. conservative treatment at 6 months
– death or major complications in 38% vs. 44% (risk ratio 0.87, 95% CI 0.64-1.18), not signi cant
but CI includes possibility of bene t or harm
● death in 7% vs. 9% (not signi cant)
● new-onset organ failure in 19% vs. 15% (not signi cant)
● pancreatic parenchymal necrosis in 15% vs. 16% (not signi cant)
● bacteremia in 15% vs. 22% (not signi cant)
● cholangitis in 2% vs. 10% (p = 0.01, NNT 13)
● pneumonia in 8% vs. 9% (not signi cant)
● pancreatic endocrine or exocrine insu ciency in 8% vs. 3% (p = 0.086)
– admission to intensive care unit (ICU) in 21% vs. 12% (p = 0.063)
– readmission for recurrent gallstone pancreatitis in 0% vs. 9% (p = 0.001, NNT 12)
– adverse events in 74% vs. 80% (no p value reported)
– ERCP-related complications in 3% vs. 3% (no p value reported)
⚬ no signi cant di erence in duration of hospital or ICU stay

⚬ Reference - APEC trial (Lancet 2020 Jul 18;396(10245):167 ), editorial can be found in Lancet 2020
Jul 18;396(10245):144
STUDY
● SUMMARY
prophylactic antibiotics may reduce bacteremia but do not appear to reduce mortality in patients
having ERCP DynaMed Level 2
COCHRANE REVIEW: Cochrane Database Syst Rev 2010 Oct 6;(10):CD007345
Details
⚬ based on Cochrane review of trials with unclear or no blinding
⚬ systematic review of 9 randomized trials comparing use of prophylactic antibiotics before ERCP to
placebo in 1,573 patients
⚬ no signi cant di erences in all-cause mortality but wide con dence intervals cannot rule out
clinical di erences
⚬ prophylactic antibiotics signi cantly reduced bacteremia in analysis of 6 trials with 579 patients
(risk ratio 0.5, 95% CI 0.33-0.78) but not in subgroup analysis of 3 trials with 309 patients where
biliary obstruction resolved with rst ERCP procedure
⚬ Reference - Cochrane Database Syst Rev 2010 Oct 6;(10):CD007345
Management of Pancreatic Fluid Collections and Pseudocyst
● intervention not required for asymptomatic pseudocysts (regardless of size, location, and/or
extension) (ACG Moderate recommendation, High-quality evidence) 1
● many pseudocysts can be managed conservatively 5
● indications for treatment 5

⚬ abdominal pain
⚬ obstruction of surrounding organs (duodenum, stomach, or bile duct)
⚬ infection
⚬ rupture
⚬ bleeding
– may occur from an associated visceral pseudoaneurysm

– bleeding may remain within pseudocyst or may reach the gut through
● spontaneous rupture with stula

● pancreatic duct (hemosuccus pancreaticus)
– treated with emergent angiography with embolization (not drainage)
● endoscopic treatment, utilizing endoscopic ultrasound guidance is primary procedure of choice for
pseudocysts with amenable anatomy 5
Management of Necrosis
Indication and Timing for Intervention
● intervention not required for asymptomatic pancreatic and/or extrapancreatic necrosis (regardless of
size, location, and/or extension) (ACG Moderate recommendation, High-quality evidence) 1
● computed tomography-guided ne-needle aspiration (CT-FNA) of pancreatic necrosis may be
necessary to distinguish infected from sterile necrosis 1

⚬ immediate review of Gram stain will often establish diagnosis
⚬ antibiotics best used only for proven infection, but may be used while awaiting culture results
⚬ need for CT-FNA in all patients uncertain because patients may improve quickly or become
unstable, and treatment with empiric antibiotics and minimally invasive approaches is an option
● for sterile necrosis
⚬ early open necrosectomy (debridement) not recommended because it is associated with increased
mortality 1
⚬ limiting and postponing surgery for severe acute pancreatitis associated with reduction in mortality
from 39% to 12% in cohort of 136 patients at one institution DynaMed Level 2 (J Gastrointest Surg
2002 May-Jun;6(3):481 )
⚬ debridement for sterile necrosis is recommended if associated with gastric outlet obstruction or
bile duct obstruction 1
● prompt surgical debridement indicated for clinically unstable patients with infected necrosis 1
● in stable patients with infected necrosis, drainage (surgical, radiologic, or endoscopic) should be
delayed for > 4 weeks to allow liquefaction of contents and development of brous wall around
necrosis (ACG Strong recommendation, Low-quality evidence) 1
● American Gastroenterological Association (AGA) recommends percutaneous drainage of pancreatic

necrosis for patients with
⚬ infected or symptomatic necrotic collections in the early, acute period (< 2 weeks)
⚬ walled-o necrosis who are too ill for endoscopic or surgical intervention
⚬ Reference - Gastroenterology 2020 Jan;158(1):67
● Eastern Association for the Surgery of Trauma recommendations for surgical management of
pancreatic necrosis
⚬ in patients with symptomatic pancreatic or peri-pancreatic necrosis
– delay surgery until day 12 and if possible, until day 30 to reduce risk of death (additional
mortality reduction not seen after day 30) (Strong recommendation based on likely patient
preference)
– provide step-up approach to surgical intervention by aggressive use of percutaneous drains to
delay or de nitively treat necrosis (based on low quality evidence)
⚬ in patients with pancreatic or peri-pancreatic necrosis, use percutaneous catheters liberally to
delay surgical intervention
⚬ Reference - J Trauma Acute Care Surg 2017 Aug;83(2):316
STUDY
● SUMMARY
delaying necrosectomy until 30 days after initial hospital admission associated with lower
mortality than earlier surgery in patients with necrotizing pancreatitis DynaMed Level 2
SYSTEMATIC REVIEW: Arch Surg 2007 Dec;142(12):1194
Details
⚬ based on systematic review of mostly observational studies
⚬ systematic review of 11 studies (10 cohort studies and 1 randomized trial) with ≥ 25 patients each
who had surgery and which evaluated timing of necrosectomy in 1,136 patients with necrotizing
pancreatitis
⚬ median time of rst surgery 26 days (range 3-31 days)
⚬ median mortality 25% (range 6%-56%)
⚬ compared with early surgery, later timing of surgery correlated with lower mortality (correlation
coe cient -0.603, 95% CI -2.1 to -0.02) in analysis of 11 studies with 1,136 patients
⚬ Reference - Arch Surg 2007 Dec;142(12):1194
STUDY
● SUMMARY
64% success rate reported with conservative treatment (that is, without necrosectomy) in
patients with infected pancreatic necrosis DynaMed Level 3
SYSTEMATIC REVIEW: Gastroenterology 2013 Feb;144(2):333
Details
⚬ based on systematic review without comparative data
⚬ systematic review of 11 observational studies and 1 randomized controlled trial evaluating primary
conservative treatment of infected pancreatic necrosis in 481 patients
⚬ analysis of randomized trial included data from treatment arm only
⚬ primary conservative treatment included intensive care, various antimicrobial agents, and
nutritional support, with or without drainage of the infected uid (percutaneous drainage rate
varied from 19% to 100%)
⚬ conservative treatment without necrosectomy evaluated in 8 studies with 324 consecutive patients
resulted in
– successful outcome (not de ned) in 64% (95% CI 51%-78%)
– subsequent surgery in 26% (95% CI 15%-37%)
– mortality in 12% (95% CI 6%-18%)
⚬ conservative treatment including percutaneous drainage evaluated in 4 studies with 157 patients
resulted in
– successful outcome in 50% (95% CI 43%-58%)
– subsequent surgery in 38% (95% CI 20%-56%)
– mortality in 18% (95% CI 6%-30%)
⚬ Reference - Gastroenterology 2013 Feb;144(2):333 , commentary can be found in

Gastroenterology 2013 Jun;144(7):1574
Method of Intervention
● American Gastroenterological Association (AGA) clinical practice guidance for drainage of pancreatic
necrosis
⚬ percutaneous drainage or transmural endoscopic drainage in patients with walled-o pancreatic
necrosis (WON)
⚬ endoscopic transmural drainage of WON may be preferred to avoid risks of forming a
pancreatocutaneous stul
⚬ direct endoscopic necrosectomy (performed at referral center with endoscopic expertise and
interventional radiology and surgical backup) for those patients with
– limited necrosis who do not adequately respond to endoscopic transmural drainage using
large-bore, self-expanding metal stents/lumen-apposing metal stents alone or plastic stents
combined with irrigation
– large amounts of infected necrosis
⚬ Reference - Gastroenterology 2020 Jan;158(1):67
● percutaneous drainage without necrosectomy may be most frequently used minimally invasive
method for managing uid collections complicating necrotizing acute pancreatitis 1
● in symptomatic patients with infected necrosis, minimally invasive methods of necrosectomy are
preferred to open necrosectomy (ACG Strong recommendation, Low-quality evidence) 1
● minimally invasive approaches for debridement of pancreatic necrosis include 1 , 2
⚬ laparoscopic surgery from anterior or retroperitoneal approach

⚬ ultrasound-guided or CT-guided percutaneous drainage and/or debridement
⚬ radiologic-guided catheter drainage or debridement
⚬ video-assisted or small incision-based left retroperitoneal debridement
⚬ transgastric or transduodenal endoscopic drainage
● open operative debridement remains an option for acute necrotizing pancreatitis in cases not
amenable to less invasive endoscopic and/or surgical procedures (Gastroenterology 2020
Jan;158(1):67 )
STUDY
● SUMMARY
endoscopic and surgical step-up approaches associated with similar risk of major complications
or death DynaMed Level 2 but endoscopic approach reduces risk of pancreatic fistula and length
of hospital stay DynaMed Level 1 in adults with infected necrotizing pancreatitis
RANDOMIZED TRIAL: Lancet 2018 Jan 6;391(10115):51

Details
⚬ based on randomized trial with wide con dence interval for primary outcome
⚬ 98 adults (mean 61 years) with infected pancreatic necrosis randomized to endoscopic step-up
approach vs. standard surgical step-up approach and followed for 6 months
– endoscopic step-up approach consisted of endoscopic ultrasound-guided transluminal drainage
followed, if necessary, by endoscopic necrosectomy (with additional percutaneous drainage
allowed)
– surgical step-up approach consisted of percutaneous catheter drainage followed, if necessary,
by video-assisted retroperitoneal debridement
⚬ patients excluded for recurrent acute pancreatitis, chronic pancreatitis, and previous invasive
treatment for necrotizing pancreatitis
⚬ primary outcome was composite of major complications (organ failure perforation of a visceral
organ requiring intervention, enterocutaneous stula requiring intervention, or incisional hernia)
and death
⚬ comparing endoscopic step-up approach vs. surgical step-up approach
– primary outcome in 43% vs. 45% (risk ratio 0.97, 95% CI 0.62-1.51), CI includes possibility of
bene t or harm
– mortality 18% vs. 13% (risk ratio 1.38, 95% CI 0.53-3.59), CI includes possibility of bene t or harm
– pancreatic stula in 5% vs. 32% (p < 0.0011, NNT 4)
– mean length of hospital stay 53 days vs. 69 days (p = 0.014)
⚬ no signi cant di erence in rates of major complications

⚬ most common adverse events were pneumonia, bacteremia, ascites, urinary tract infection,
cholecystitis or cholangitis and atrial brillation
⚬ Reference - Lancet 2018 Jan 6;391(10115):51 , editorial can be found in Lancet 2018 Jan
6;391(10115):6
EVIDENCE SYNOPSIS
Percutaneous or endoscopic transgastric drainage in a step-up approach may reduce new-onset

multiple organ failure and reduce major complications and death compared to open necrosectomy
in patients with infected necrotizing pancreatitis based on 2 randomized trials and 1 long-term
follow up suggests.
STUDY
⚬ SUMMARY
percutaneous or endoscopic transgastric drainage as initial treatment (step-up approach)
reduces new-onset multiple organ failure and diabetes compared to open necrosectomy in
patients with infected necrotizing pancreatitis and infected necrotic tissue DynaMed Level 1
RANDOMIZED TRIAL: N Engl J Med 2010 Apr 22;362(16):1491 | Full Text
Details
– based on randomized trial
– 88 patients with necrotizing pancreatitis and suspected or con rmed infected necrotic tissue
randomized to percutaneous or endoscopic transgastric drainage as initial treatment (step-up
approach) vs. primary open necrosectomy
– step-up approach de ned as percutaneous or endoscopic transgastric drainage followed by
minimally invasive retroperitoneal necrosectomy if necessary
– 35% having step-up approach treated with percutaneous drainage only
– comparing step-up approach vs. open necrosectomy
● primary end-point (composite of major complications or death) in 17 of 43 patients (40%)

vs. 31 of 45 patients (69%) (p = 0.006, NNT 4)
● major complications at 3 months
⚬ new-onset multiple-organ failure in 12% vs. 42% (p = 0.002, NNT 4)

⚬ intraabdominal bleeding requiring intervention in 16% vs. 22% (not signi cant)
⚬ enterocutaneous stula or perforation of visceral organ requiring intervention in 14% vs.
22% (not signi cant)
● other complications at 6 months
⚬ incisional hernia in 7% vs. 24% (p = 0.03, NNT 6) at

⚬ new-onset diabetes requiring medications 6 months after discharge in 16% vs. 38% (p =
0.02, NNT 5)
● death in 19% vs. 16% (not signi cant)
– Reference - PANTER trial (N Engl J Med 2010 Apr 22;362(16):1491 full-text ), editorial can
be found in N Engl J Med 2010 Apr 22;362(16):1535
STUDY
⚬ SUMMARY
benefits of step-up approach (percutaneous or endoscopic transgastric drainage) as initial
treatment for necrotizing pancreatitis appear to be maintained at long term follow-up of
mean 7 years DynaMed Level 2
RANDOMIZED TRIAL: Gastroenterology 2019 Mar;156(4):1016
Details
– based on long-term follow-up of PANTER trial
– 83% (73) patients alive after index admission were evaluated
– follow up at mean 86 months (range 75- 97 months)
– comparing step-up approach vs. open necrosectomy
● primary outcome (composite of major complications or death for all 88 patients originally
enrolled) in 44% vs. 73% (p = 0.005, NNT 4)
● among 75 patients alive at beginning of follow-up
⚬ pancreatic exocrine insu ciency in 29% vs. 56% (p = 0.03, NNT 4)

⚬ incisional hernia in 20% vs. 50% (p = 0.03, NNT 4)
⚬ endocrine insu ciency in 40% vs. 64% (p = 0.05. NNT 5)
⚬ additional drainage procedure required in 11% vs. 13% (not signi cant)
⚬ additional pancreatic surgery in 11% vs. 5% (not signi cant)
– no signi cant di erence in recurrent acute pancreatitis, chronic pancreatitis, Izbicki pain-
scores, or increase in quality of life
– Reference - Gastroenterology 2019 Mar;156(4):1016 , editorial can be found in
Gastroenterology 2019 Mar;156(4):867 , commentary can be found in Gastroenterology
2019 Sep;157(3):892
STUDY
⚬ SUMMARY
endoscopic transgastric necrosectomy may reduce new-onset multiple organ failure
compared to surgical necrosectomy in patients with infected necrotizing pancreatitis
DynaMed Level 2
RANDOMIZED TRIAL: JAMA 2012 Mar 14;307(10):1053
Details
– based on small randomized trial
– 22 patients (median age 62-64 years) with suspected or con rmed infected necrotizing
pancreatitis randomized to endoscopic transgastric necrosectomy vs. surgical necrosectomy
● endoscopic transgastric necrosectomy included transgastric puncture, balloon dilatation,
retroperitoneal drainage, and necrosectomy
● surgical necrosectomy included video-assisted retroperitoneal debridement or laparotomy
– 91% had necrosectomy and were included in analyses

– comparing endoscopic transgastric necrosectomy vs. surgical necrosectomy
● new-onset multiple organ failure in 0% vs. 50% (p = 0.03, NNT 2)

● pancreatic stula in 10% vs. 70% (p = 0.02, NNT 2)
● 6-month mortality 10% vs. 40% (not signi cant)
– Reference - JAMA 2012 Mar 14;307(10):1053 , editorial can be found in JAMA 2012 Mar
14;307(10):1084
● Cochrane review of interventions for necrotizing pancreatitis can be found in Cochrane Database Syst
Rev 2016 Apr 16;(4):CD011383
Cholecystectomy
● in acute biliary pancreatitis, cholecystectomy recommended during the initial admission rather than
after discharge (AGA Strong recommendation, Moderate-quality evidence) (ACG Moderate
recommendation, Moderate-quality evidence) 4 , 1
● in necrotizing biliary acute pancreatitis, cholecystectomy should be deferred until active in ammation
subsides and uid collections resolve or stabilize, to prevent infection (ACG Strong recommendation,
Moderate-quality evidence) 1
● for gallstone pancreatitis optimal timing of cholecystectomy after hospital admission may be within 48
hours for mild disease and > 2 weeks later for more severe disease DynaMed Level 2
STUDY
● SUMMARY
laparoscopic cholecystectomy for idiopathic pancreatitis may reduce recurrence of pancreatitis
in adults DynaMed Level 2
RANDOMIZED TRIAL: Ann Surg 2015 Nov;262(5):736
Details
⚬ based on randomized trial with early termination
⚬ 85 adult patients who had rst attack of idiopathic pancreatitis randomized to laparoscopic
cholecystectomy vs. observation with median follow-up of 36 months (range 5–58 months)
⚬ initial power calculation speci ed 154 patients, but interim safety analysis after 4 years showed
bene t of cholecystectomy and trial was terminated
⚬ comparing laparoscopic cholecystectomy vs. observation
– patients with recurrences of pancreatitis 4 (10%) vs. 14 (30%) (p = 0.016, NNT 5)

– total number of recurrences 8 vs. 23 (p = 0.003)
⚬ in subgroup analysis of patients having laparoscopic cholecystectomy, 23 of 39 patients (59%) had

biliary stones or sludge not previously identi ed
⚬ Reference - Ann Surg 2015 Nov;262(5):736
● see Cholecystectomy for additional information
Peritoneal Lavage
EVIDENCE SYNOPSIS
Older systematic reviews of trials prior to 2010 suggested peritoneal lavage may not be bene cial,
but a more recent SR with additional trials (only 3 of 15 trials in older systematic review) and more
rigorous evaluation of study quality shows peritoneal lavage may reduce mortality and
complications in patients with severe acute pancreatitis.
STUDY
⚬ SUMMARY
peritoneal lavage may reduce mortality and pancreatitis-related complications in patients
with severe acute pancreatitis compared to standard care DynaMed Level 2
SYSTEMATIC REVIEW: Pancreas 2016 Jul;45(6):806
Details
– systematic review of 15 randomized trials comparing continuous peritoneal lavage to
conservative treatment for severe acute pancreatitis in 899 patients
– conservative treatment included initial fasting, uid resuscitation, protease inhibitor,
nutritional support, antibiotics prophylaxis, and pain control
– diagnosis of severe acute pancreatitis by Atlanta criteria or combination of clinical features,
biochemical tests, and imaging studies
– methodologic limitations included

● inadequate allocation concealment in 13 trials
● selective outcome reporting in 11 trials
● high drop out rates in 3 trials
– compared to standard care, continuous peritoneal lavage associated with decreased
● all-cause mortality (pooled relative risk [RR] 0.47, 95% CI 0.34-0.66) in analysis of 12 trials
with 810 patients
● pancreatitis-related overall complications (pooled RR 0.63, 95% CI 0.48-0.83) in analysis of 9
trials with 488 patients
● acute renal failure (pooled RR 0.27, 95% CI 0.12-0.61) in analysis of 3 trials with 171 patients
● acute respiratory distress syndrome (pooled RR 0.17, 95% CI 0.05-0.65) in analysis of 4 trials
with 260 patients
● cardiovascular complications (pooled RR 0.38, 95% CI 0.2-0.71) in analysis of 3 trials with
171 patients
● need for operation (pooled RR 0.24, 95% CI 0.1-0.58) in analysis of 2 trials with 141 patients
● length of hospital stay (pooled mean di erence 12.9 fewer days, 95% CI 7.7 to 18.2 fewer
days) in analysis of 10 trials with 576 patients, results limited by heterogeneity
– no procedure or infectious complications of lavage treatment reported in all trials
– Reference - Pancreas 2016 Jul;45(6):806
STUDY
⚬ SUMMARY
peritoneal lavage does not appear to reduce mortality or complications in patients with
SYSTEMATIC REVIEW: World J Surg 2010 Sep;34(9):2103
Details
– systematic review of 10 randomized trials evaluating peritoneal lavage vs. conservative
treatment or pancreatic resection in 469 patients with severe acute pancreatitis
– methodologic limitations included
● unclear blinding in 9 studies

● unclear allocation concealment in 4 trials
– no signi cant di erences found between groups in
● mortality in analysis of 4 trials with 257 patients

● complications in analysis of 3 trials with 153 patients
● hospital stay
– Reference - World J Surg 2010 Sep;34(9):2103
Consultation and Referral
● if complications present, need coordinated care of team of physicians and healthcare personnel,
including 5
⚬ surgeons
⚬ radiologists
⚬ gastroenterologists
⚬ critical care specialists
● management of infected pancreatic necrosis may require 5
⚬ group of experienced clinicians

⚬ referral to a major specialist center if local resources not available
● refer patients with idiopathic pancreatitis to centers of expertise (ACG Conditional recommendation,
Low-quality evidence) 1
● refer patients with a suspected genetic basis for their pancreatitis to a genetics counselor before
testing 5
Other Management
Nasogastric Suction
● no evidence to support e ectiveness in decreasing symptoms, mortality, or hospital stay 5
● may be bene cial for nausea and vomiting 5
Treatment of Acute Hypertriglyceridemic Pancreatitis
● treatment options in patients with severe hypertriglyceridemic acute pancreatitis with either limited
evidence of e cacy or availability include
⚬ apheresis - reported to rapidly reduce serum chylomicron and triglyceride levels
⚬ insulin - reported to activate lipoprotein lipase, which causes increased chylomicron degradation,
and may be used to lower serum triglycerides
⚬ unfractionated heparin - reported to stimulate release of lipoprotein lipase from endothelial cells,
but use remains controversial as increase in lipoprotein lipase activity is transient and usually
followed by rapid depletion in lipoprotein lipase plasma stores
⚬ brates - reported to lower serum triglycerides due to increased lipoprotein lipase activity and
decreased hepatic triglyceride synthesis
⚬ Reference - United European Gastroenterol J 2018 Jun;6(5):649 full-text
● role of therapeutic plasma exchange (TPE) not established for
⚬ severe hypertriglyceridemic pancreatitis (ASFA Category III, Grade 1C)

⚬ prevention of hypertriglyceridemic pancreatitis relapse (ASFA Category III, Grade 2C)
⚬ Reference - American Society for Apheresis (ASFA) guideline on use of therapeutic apheresis in
clinical practice (J Clin Apher 2019 Jun;34(3):171 )
● TPE reported to reduce extreme elevations of triglyceride levels in case series of patients with
hypertriglyceridemic acute pancreatitis
STUDY
⚬ SUMMARY
plasmapheresis reported to lower triglyceride levels in patients with hypertriglyceridemia-
induced pancreatitis DynaMed Level 3
CASE SERIES: J Clin Apher 2010;25(4):229
Details
– based on case series
– 4 patients with hyperlipidemic pancreatitis had insulin or heparin infusion, antibiotics, and lipid-
lowering agents, and were treated with plasmapheresis with 5% albumin within rst 48 hours of
admission
– plasmapheresis associated with average reduction of triglyceride levels 70.4% per treatment
and 89.3% with rst treatment
– Reference - J Clin Apher 2010;25(4):229
⚬ double ltration plasmapheresis reported to reduce hypertriglyceridemia associated with acute
pancreatitis in case series of 3 patients (Medicine (Baltimore) 2018 Nov;97(44):e12987 )
STUDY
⚬ SUMMARY
hemoperfusion plus additional therapy (Penta-association therapy) reported to be effective
for treatment of severe acute hyperlipidemic pancreatitis DynaMed Level 3
CASE SERIES: World J Gastroenterol 2003 Nov;9(11):2622 | Full Text
Details
– 32 consecutive patients with hyperlipidemic severe acute pancreatitis were treated with
conventional therapy plus Penta-association therapy and evaluated after end of therapy and
after 7 days
– patients had APACHE II score > 8, time to intervention < 72 hours after disease onset, serum
triglycerides ≥ 602.5 mg/dL (6.8 mmol/L), and exclusion of other etiologies
– Penta-associated therapy included
● hemo ltration and triglyceride adsorption

● uvastatin or feno brate
● low-molecular-weight heparin
● insulin
● topical Pixiao (traditional Chinese medicine) over abdomen
– compared with baseline, posttreatment serum triglyceride levels and APACHE II scores
signi cantly decreased (p < 0.05)
– Reference - World J Gastroenterol 2003 Nov;9(11):2622 full-text
STUDY
⚬ SUMMARY
plasma exchange, if applied promptly, reported to be effective for patients with
hypertriglyceridemic acute necrotizing pancreatitis DynaMed Level 3
CASE SERIES: Ther Apher 2002 Dec;6(6):454
Details
– 2 patients with acute necrotizing pancreatitis were treated with plasma exchange
● 1 patient and triglyceride level 3,540 mg/dL treated quickly had normalization of triglyceride
levels and survived
● 1 patient with triglyceride level 6,460 mg/dL treated after 20 days and died
– Reference - Ther Apher 2002 Dec;6(6):454
⚬ IV heparin and insulin reported to rapidly reduce extreme elevations in serum triglyceride levels in
patients with acute pancreatitis in case reports
– case report of hypertriglyceridemia-induced acute pancreatitis treated with heparin and insulin
can be found in Indian J Gastroenterol 2003 May-Jun;22(3):102
– case report of heparin and insulin for hypertriglyceridemia-induced acute pancreatitis with
triglyceride level 10,320 mg/dL can be found in Scienti cWorldJournal 2009 Nov 1;9:1230 PDF
– case report of heparin treatment for severe hypertriglyceridemia in patient with diabetic
ketoacidosis can be found in Arch Intern Med 2009 Aug 10;169(15):1439 , commentary can be
found in Arch Intern Med 2010 Jan 11;170(1):108
● see also Hypertriglyceridemia for detailed information
Complications and Prognosis
Complications
● local complications 1 , 2 , 3 , 6
⚬ pancreatic local complications (described in Image-based classi cation of pancreatic local

complications)
– acute peripancreatic fluid collection (APFC) - uid collection without encapsulation
– pancreatic pseudocyst - encapsulated uid collection without necrosis; see Pancreatic
Pseudocyst for information
– necrotizing pancreatitis - pancreatic or peripancreatic necrosis, occurs in 5%-10% of patients
(Nat Rev Gastroenterol Hepatol 2019 Aug;16(8):479 )
– acute necrotic collection (ANC) - contains both uid and necrosis
– walled-o necrosis (WON) - may be multiple, infected, and occur at sites distant from pancreas
⚬ other local complications
– gastric outlet dysfunction

– splenic and portal vein thrombosis
– abdominal compartment syndrome
– pancreatic arterial pseudoaneurysms
● systemic complications
⚬ de ned as failure of an organ system or exacerbation of preexisting disorder, such as chronic
obstructive pulmonary disease, heart failure, or chronic liver disease 3

⚬ vascular complications
– uid losses (hypovolemia)

– shock
– pancreatic ascites
– hypotension
– Reference - Lancet 2008 Jan 12;371(9607):143
⚬ respiratory complications 1
– hypoxemia
– pleural e usion
– acute respiratory distress syndrome (ARDS)
– pulmonary complications in 15%-55% with severe pancreatitis, and can include mild hypoxemia
to severe acute respiratory distress syndrome (Lancet 2008 Jan 12;371(9607):143 )
⚬ renal complications, due to 3
– inadequate uid resuscitation

– sepsis
⚬ hepatic complications
– mild hepatic injury, contributing to systemic in ammatory responses (Lancet 2008 Jan
12;371(9607):143 )
– exacerbation of pre-existing chronic liver disease 3
⚬ metabolic complications 6
– hypocalcemia
– hypomagnesemia
– hyperglycemia
⚬ intestinal complications 6
– bowel infarction
– ileus
– colonic necrosis
● 40% of patients with acute pancreatitis develop new-onset prediabetes or diabetes following rst
episode of acute pancreatitis (Nat Rev Gastroenterol Hepatol 2019 Aug;16(8):479 )
● 25% of all patients with acute pancreatitis develop exocrine pancreatic insu ciency (Nat Rev
Gastroenterol Hepatol 2019 Aug;16(8):479 )
STUDY
● SUMMARY
maternal mortality 3.6% and fetal mortality 32.5% in women with severe acute pancreatitis
during pregnancy
COHORT STUDY: Postgrad Med 2020 Apr 17;early online
Details
⚬ 96,132 pregnant women including 215 women diagnosed with acute pancreatitis and 83 women
diagnosed with severe acute pancreatitis were evaluated for association between acute
pancreatitis and maternal complications using medical records at single center from 2012 to 2017
⚬ diagnosis criteria were according to revised Atlanta Criteria of 2012
⚬ among 83 women with severe acute pancreatitis in pregnancy
– maternal mortality 3.6% (3 women died)

– fetal mortality 32.5% (27 women had fetal loss)
– incidence of fetal loss in
● rst trimester 100% (1 woman)

● second trimester, 63.6% (7 of 11 women)
● third trimester, 26.8% (19 of 71 women)
– identi ed cause of severe acute pancreatitis
● 24.1% acute biliary pancreatitis (20 women)

● 49.4% hypertriglyceridemia pancreatitis (41 women)
● 26.5% hyperparathyroidism, ketoacidosis, and idiopathic (22 women)
– maternal complications or factors associated with fetal loss
● hypertriglyceridemia (odds ratio [OR] 3.48, 95% CI 2.15-6.67)

● time from onset to diagnosis (OR 2.31, 95% CI 1.96-2.97)
● major organ failure (OR 6.58, 95% CI 2.23-9.87)
● gestational diabetes mellitus (OR 5.85, 95% CI 3.04-8.66)
pre-eclampsia (OR 6.35, 95% CI 3.67-8.97)
●
⚬ Reference - Postgrad Med 2020 Apr 17;early online
Prognosis
General Prognosis
● mild acute pancreatitis typically resolves in a few days 6
● 15%-20% develop complications 3
● clinical factors that appear associated with more severe course include 1
⚬ age > 55 years

⚬ obesity (BMI > 30 kg/m2 )
⚬ altered mental status

⚬ comorbid disease
⚬ systemic in ammatory response syndrome (SIRS)
⚬ > 2 of the following - pulse > 90 beats/minute, respirations > 20/minute or PaCO2 > 32 mm Hg,
temperature > 38 °C or < 36 °C, WBC count > 12,000 cells/mm3 or < 4,000 cells/mm3, or > 10%
immature neutrophils (bands)
⚬ BUN > 20 mg/dL
⚬ rising BUN
⚬ hematocrit > 44%
⚬ rising HCT
⚬ elevated creatinine
⚬ x-ray ndings of pleural e usions, pulmonary in ltrates, or multiple or extensive extrapancreatic
collections
⚬ arterial lactate ≥ 4 mmol/L (BMC Gastroenterol 2020 Apr 19;20(1):116 full-text )
● mortality in acute pancreatitis
⚬ overall mortality decreasing over the past decade from 1.6% to 0.8% (Nat Rev Gastroenterol
Hepatol 2019 Aug;16(8):479 )
⚬ in mild acute pancreatitis < 2% mortality 3
⚬ in moderately severe acute pancreatitis < 5% mortality 3
⚬ increased mortality in severe acute pancreatitis (up to 30% mortality) 6
– sterile necrosis (10%) 3
– infected necrosis (30%) 3
● infected necrosis without persistent organ failure associated with lesser mortality rate than
infected necrosis with persistent organ failure 2
STUDY
– SUMMARY
severe acute pancreatitis associated with 17.9% overall 90-day mortality
COHORT STUDY: J Crit Care 2019 Oct;53:81
Details
● based on retrospective cohort study
● 435 adults with severe acute pancreatitis treated in intensive care unit and followed for 90
days
● 90-day survival 82.1% (357 patients) after hospital admission
● among patients who died, cause of death was acute pancreatitis in 98.7% within 90 days after
hospital admission
● factors associated with increased 90-day mortality
⚬ age > 69 years (OR 10.4, 95% CI 4.1-26.2)

⚬ age 60-69 years (odds ratio [OR] 5.1, 95% CI 2.5-10.6)
⚬ female sex (OR 2, 95% CI 1-4.1)
⚬ heart disease (OR 2.9, 95% CI 1.4-5.9)
⚬ chronic liver failure (OR 12.3, 95% CI 1.8-96.7)
⚬ sterile necrosectomy within 4 weeks (OR 14.7, 95% CI 4.4-48.8)
● Reference - J Crit Care 2019 Oct;53:81
– organ failure within rst days of disease (36%-50% mortality) 2
STUDY
● SUMMARY
organ failure and infection of pancreatic necrosis associated with ≥ 30% mortality in
SYSTEMATIC REVIEW: Gastroenterology 2010 Sep;139(3):813
Details
⚬ systematic review of 14 cohort studies with 1,478 patients with acute pancreatitis
evaluated for mortality
⚬ overall mortality 13%, including
– 179 patients (30%) of 600 patients with organ failure (mortality in pooled analysis)
– 102 patients (32%) of 314 patients with infection of pancreatic necrosis
⚬ compared with patients with organ failure and no infection of pancreatic necrosis, organ
failure and infection of pancreatic necrosis associated with increased risk of death (risk
ratio 1.94, 95% CI:1.32-2.85)
⚬ compared with patients with infection of pancreatic necrosis and no organ failure, organ
failure and infection of pancreatic necrosis associated with increased risk of death (risk
ratio 2.65, 95% CI 1.3-5.4)
⚬ Reference - Gastroenterology 2010 Sep;139(3):813
STUDY
● SUMMARY
severe acute pancreatitis (persistent organ failure after 48 hours) associated with high
risk of mortality
COHORT STUDY: Indian J Crit Care Med 2020 Feb;24(2):99 | Full Text
Details
⚬ based on prospective cohort study
⚬ 87 patients (mean age 38 years, 86% men) presenting with rst attack of acute
pancreatitis were evaluated at presentation and followed during hospital stay until
discharge, death, or clinical cure
⚬ severity of acute pancreatitis determined as per 2012 revision of Atlanta classi cation with
focus on organ failure and complications criteria
⚬ organ failure de ned as score of ≥ 2 for any 1 of 2 major organ systems (respiratory,
cardiovascular, and renal) using modi ed Marshall scoring system
⚬ severity in patients with rst attack of acute pancreatitis
– 23% severe acute pancreatitis (20 patients)

– 10.3% moderately severe acute pancreatitis (9 patients)
– 66.7% mild acute pancreatitis (58 patients)
⚬ overall mortality 12.64% in patients with acute pancreatitis (11 deaths in 87 patients)
⚬ mortality 50% in patients with severe acute pancreatitis (10 deaths in 20 patients)
⚬ comparing patients with mild and moderately severe acute pancreatitis vs. patients with
severe acute pancreatitis
– APACHE II score 11.35 vs. 4.31 (p < 0.001)
– modi ed CTSI score 8.4 vs. 5.85 (p < 0.001)
– BISAP score 2.5 vs. 1.03 (p < 0.001)
⚬ Reference - Indian J Crit Care Med 2020 Feb;24(2):99 full-text
● about 18% of patients with acute pancreatitis experience recurrence, and 8% develop chronic
pancreatitis (Nat Rev Gastroenterol Hepatol 2019 Aug;16(8):479 )
● majority of patients with single episode of unexplained acute pancreatitis do not have a second
attack 5
● prognosis variable for moderately severe pancreatitis 1 , 2
⚬ may resolve without intervention

⚬ may require prolonged specialist care (as in extensive sterile necrosis without organ failure)
⚬ lower mortality than severe acute pancreatitis
● most pancreatic uid collections resolve 5
⚬ 50% resolve in < 6 weeks

⚬ 15% persist as pseudocysts, which may eventually seal o spontaneously and lead to spontaneous
regression
STUDY
● SUMMARY
readmission for acute pancreatitis 29% and for chronic pancreatitis 13% following first attack of
acute pancreatitis
COHORT STUDY: Am J Gastroenterol 2012 Jul;107(7):1096
Details
⚬ 84% of 7,456 patients (mean age 58 years) with rst attack of acute pancreatitis (36% idiopathic,
28% biliary, and 19% alcohol-associated) from 1996 to 2005 were followed for median 40 months
after discharge
⚬ readmission rates
– 29% for any acute pancreatitis

– 13% any chronic pancreatitis
⚬ increased risk of chronic pancreatitis signi cantly associated with
– alcoholic pancreatitis
– tobacco use
– recurrence of acute pancreatitis
⚬ Reference - Am J Gastroenterol 2012 Jul;107(7):1096
STUDY
● SUMMARY
acute pancreatitis due to alcoholism associated with increased risk of progression to chronic
pancreatitis
COHORT STUDY: Am J Gastroenterol 2009 Nov;104(11):2797
Details
⚬ 532 patients hospitalized after initial acute pancreatitis were followed for average 7.8 years
⚬ 16.5% developed recurrent pancreatitis (attributed to alcoholism, gallstones and other causes)
⚬ chronic pancreatitis developed only in patients with alcoholism
⚬ compared with no smoking, smoking associated with increased risk of progression to chronic
pancreatitis among patients with alcoholism (hazard ratio 4.3, 95% Ci 1.11– 6.6)
⚬ Reference - Am J Gastroenterol 2009 Nov;104(11):2797
STUDY
● SUMMARY
acute pancreatitis due to alcoholism associated with increased risk of recurrent acute
pancreatitis and progression to chronic pancreatitis
COHORT STUDY: Scand J Gastroenterol 2019 Jan;54(1):87
Details
⚬ 1,102 adults (mean age 56 years) with rst-time acute pancreatitis from 2006-2015 in Iceland were
retrospectively evaluated for diagnosis of chronic or recurrent pancreatitis during mean follow-up 4
years in medical records
⚬ 6% (64 adults) had severe pancreatitis according to Atlanta classi cation
⚬ recurrent acute pancreatitis (≥ 1 episode) in 21% (225 adults) of adults surviving rst-time acute
pancreatitis during follow-up; chronic pancreatitis developed in 3.7% during follow-up
⚬ highest rates of recurrence in adults with rst-time pancreatitis due to alcohol use
⚬ factors associated with increased recurrent acute pancreatitis
– alcohol use (vs. biliary cause hazard ratio (HR) 2.29, 95% CI 1.51-3.46)
– male gender (HR 1.48, 95% CI 1.08-2.04)
– smoking (HR 1.62, 95% CI 1.15-2.28)
⚬ factors associated with increased development of chronic pancreatitis
– alcohol use (vs. biliary cause HR 9.16, 95% CI 2.71-30.9)

– recurrent acute pancreatitis (HR 8.79, 95% CI 3.94-19.62)
– local complications (HR 4.77, 95% CI 1.93-11.79)
– organ-failure (HR 2.86, 95% CI 1.1-7.42)
⚬ Reference - Scand J Gastroenterol 2019 Jan;54(1):87
Prognostic Scoring Systems

● several prognostic scoring systems have been developed to assess risk in acute pancreatitis, however,
in clinical situations, their utility may be limited 1
● World Congress of Emergency Surgery consensus guidelines on management of severe acute

pancreatitis recommend bedside index of severity in acute pancreatitis (BISAP) score for simplicity in
everyday clinical practice and ability to predict severity, death, and organ failure, as well as APACHE-II
score (more complex), although no evidence indicates any prognostic score superior (World J Emerg
Surg 2019;14:27 full-text )
STUDY
● SUMMARY
insufficient evidence to determine superior predictive abilities between Pancreatitis Outcome
Prediction (POP), Sequential Organ Failure Assessment (SOFA), bedside index of severity in acute
pancreatitis (BISAP), Ranson criteria, Acute Physiology and Chronic Health Evaluation II
(APACHE II) score and other clinical severity scores in adults with acute pancreatitis
SYSTEMATIC REVIEW: Ann Intern Med 2016 Oct 4;165(7):482
Details
⚬ based on systematic review limited by clinical heterogeneity
⚬ systematic review of 94 prognostic studies evaluating 18 clinical severity scores for predicting
mortality in 53,547 adults with acute pancreatitis
⚬ meta-analyses not performed due to clinical heterogeneity and inadequate study methodology and
outcome reporting quality
⚬ performance of severity scores for prediction of mortality
– Pancreatitis Outcome Prediction (POP) score with cuto > 13 had median sensitivity 88.3%
(range 86.7%-90%) and median speci city 88.5% (range 85%-92%) in 2 studies with 308 patients
– Sequential Organ Failure Assessment (SOFA) score with cuto > 8 had median sensitivity 86.6%
(range 0%-95.3%) and median speci city 87.2% (range 41.4%-90.9%) in 5 studies with 258
patients
– bedside index of severity in acute pancreatitis (BISAP) score with cuto > 2 had median
sensitivity 71.4% (range 33.3%-100%) and median speci city 87.6% (range 62.9%-97.6%) in 17
studies with 21,733 patients
– Ranson criteria with cuto > 2 had median sensitivity 90% (range 0%-100%) and median
speci city 67.4% (range 13.6%-97%) in 26 studies with 3,539 patients
– Acute Physiology and Chronic Health Evaluation II (APACHE II) score with cuto > 7 had median
sensitivity 100% (range 67.7%-100%) and median speci city 63.4% (range 21.4%-95.9%) in 13
studies with 2,452 patients
– systemic in ammatory response syndrome (SIRS) score with cuto > 1 had median sensitivity
100% (range 33.3%-100%) and median speci city 59.6% (range 15.5%-78.2%) in 9 studies with
1,227 patients
– Japanese Severity Score (revised) with cuto > 4 had median sensitivity 50.4% (range 0%-100%)
and median speci city 87.3% (range 69.6%-99%) in 4 studies with 18,227 patients
– Glasgow criteria with cuto > 3 had median sensitivity 50% (range 29.4%-100%) and median
speci city 78.6% (range 27%-96.9%) in 9 studies with 1,659 patients
– Multiple Organ Dysfunction Score with cuto > 8 had median sensitivity 25% (range
21.9%-93.3%) and median speci city 91.7% (range 78.7%-98.3%) in 3 studies with 182 patients
⚬ Reference - Ann Intern Med 2016 Oct 4;165(7):482 , editorial can be found in Ann Intern Med
2016 Oct 4;165(7):523 full-text
⚬
DynaMed Commentary
In this systematic review, the authors concluded that the available evidence does not provide
clear guidance on which models should be used in speci c patient populations, nor direct
speci c therapy to achieve improved clinical outcomes in acute pancreatitis. A commentary on
multiple-factor clinical scoring systems for predicting prognosis in acute pancreatitis can be
found in Ann Intern Med 2016 Oct 4;165(7):523 .full-text
● other prognostic scoring systems
⚬ BALI score
– BALI score derived from 4 criteria measured at admission 6
● BUN ≥ 25 mg/dL (8.9 mmol per L)

● Age ≥ 65 years
● LDH ≥ 300 units/L
● interleukin-6 (IL-6) ≥ 300 pg/mL
STUDY
– SUMMARY
BALI criteria may predict mortality at 90 days DynaMed Level 2
DIAGNOSTIC COHORT STUDY: Ann Surg 2006 Mar;243(3):380
Details
● based on derivation and validation cohort study without independent validation cohort
● 1,518 patients participated in randomized placebo-controlled trial of lexipafant within 48
hours of pancreatitis
⚬ 149 (9.8%) died within 90 days
⚬ serum samples for cytokines IL-6 and IL-8 obtained from rst 450 patients
⚬ two-thirds sample used for predictive model development and one-third sample for
validation
● BALI model used 4 variables from initial evaluation
⚬ BUN 25 mg/dL or higher

⚬ age 65 years or higher
⚬ LDH 300 units/L or higher
⚬ IL-6 300 pg/mL or higher
● mortality based on number of positive BALI factors in analysis of 365 patients (of whom 40
died)
⚬ 0 if 0 factors
⚬ 5% if 1-2 factors
⚬ 27% if 3 factors
⚬ 54% if 4 factors
● prognostic ability similar in this sample for BALI, Ranson, Glasgow and APACHE II criteria (but
this was the sample set used to derive the BALI model)
● Reference - Ann Surg 2006 Mar;243(3):380
⚬ Modi ed Marshall Scoring System for Organ Dysfunction 2

– organ failure de ned as score ≥ 2 in any column listed in table
Table 1. Modified Marshall Scoring System for Organ System Dysfunction
Score PaO2/FiO2* Serum Cardiovascula

Creatinine** r Status***
0 > 400 mm Hg ≤ 134 mcmol/L (< SBP > 90 mm

1.4 mg/dL) Hg
1 301-400 mm Hg 134-169 mcmol/L ● SBP < 90

(1.4-1.8 mg/dL) mm Hg
● Fluid
responsive
2 201-300 mm Hg 170-310 mcmol/L ● SBP < 90

(1.9-3.6 mg/dL) mm Hg
● Not uid
responsive
3 101-200 mm Hg 311-349 mcmol/L ● SBP < 90

(3.6-4.9 mg/dL) mm Hg
● pH < 7.3
4 ≤ 101 mm Hg > 439 mcmol/L (> ● SBP < 90

4.9 mg/dL) mm Hg
● pH < 7.2
Abbreviations: FIO2, fraction of inspired oxygen; PaO2, partial pressure of oxygen in

arterial blood; SBP, systolic blood pressure.* Estimated FiO2 for nonventilated patients:
● Room air - 21%

● Supplemental oxygen 2 L/minute - 25%
● Supplemental oxygen 4 L/minute - 30%
● Supplemental oxygen 6-8 L/minute - 40%
● Supplemental oxygen 9-10 L/minute - 50%
** Score for patients with preexisting chronic renal failure depends on extent of further
deterioration of baseline renal function. No formal correction exists for a baseline serum
creatinine ≥ 134 mmol/L (≥ 1.4 mg/dL).*** O inotropic support.
STUDY
⚬ SUMMARY
scoring system based on 4 parameters (increased lactate dehydrogenase (LDH), creatinine
(Cr), albumin (ALB), and calcium (Ca2+) levels at admission may predict organ failure and
mortality in patients with acute pancreatitis DynaMed Level 2
COHORT STUDY: Pancreatology 2020 Jun;20(4):622
Details
– based on prognostic cohort study with independent retrospective derivation cohort and small
prospective validation cohort
– derivation cohort included 1,076 patients (median age 45 years) with acute pancreatitis
– all laboratory parameters measured at admission (within 72 hours of disease onset)
– 84 patients died of organ failure (7.8%), 240 had persistent organ failure and survived, 628 had
transient organ failure and 124 no organ failure
– clinical prediction rule derived using factors signi cantly associated with organ failure in
derivation cohort included increased lactate dehydrogenase (LDH), creatinine (Cr), albumin
(ALB), and calcium (Ca2+) levels at admission (WL score, each parameter scored 0-3 using
derived cut-o values, for total score of 0-12)
TOF Cut-o POF Cut-o Death Cut-o

(Score = 1) (Score = 2) (Score = 3)
LDH 270.5 346.5 404.5
Cr 69.65 73.85 110.65
ALB 35.85 33.45 32.05
CA2+ 2.115 1.955 1.665
Abbreviations: TOF, transient organ failure; POF, persistent organ failure.
Reference - Pancreatology 2020 Jun;20(4):622
– validation cohort included 138 patients (median age 48 years) with acute pancreatitis
– 14 patients died of organ failure (10.1%), 37 had persistent organ failure and survived, 72 had
transient organ failure and 15 no organ failure
– for prediction of any organ failure (transient or persistent organ failure, with survival or death)
WL total score > 0.5 had
● sensitivity 92.7%
● speci city 86.7%
● positive predictive value 98.3%
● negative predictive value 59.1%
– for prediction of persistent organ failure (including death from persistent organ failure) WL
score > 4.5 had
– for prediction of death WL score > 9.5 had
– Reference - Pancreatology 2020 Jun;20(4):622
STUDY
⚬ SUMMARY
Atlanta reclassification system (2012) and determinant-based classification system predict
intensive care unit admission and need for intervention in patients with acute pancreatitis
DynaMed Level 1
COHORT STUDY: Am J Gastroenterol 2013 Dec;108(12):1911
Details
– based on validation cohort study
– 256 patients (median age 51 years) with acute pancreatitis were classi ed using 3 di erent
classi cation systems and followed until hospital discharge and during subsequent admissions
Classi cati Mild Moderate Severe Critical

on System
Atlanta No local N/A Local N/A

classi catio complicatio complicatio
n (1992) ns or organ ns and/or
failure; organ
APACHE II failure
score < 8 and/or
and Ranson APACHE II
criteria < 3 score ≥ 8 or
Ranson
criteria ≥ 3
Atlanta No local Local Persistent N/A

reclassi cati complicatio complicatio organ
on (2012) ns or organ ns and/or failure > 48
failure transient hours
organ
failure
Classi cati Mild Moderate Severe Critical
on System
Determinan No Sterile Infected Infected

t-based peripancrea peripancrea peripancrea peripancrea
classi catio tic necrosis tic necrosis tic necrosis titis
n and no and/or OR necrosis
organ transient persistent AND
failure organ organ persistent
failure failure organ
failure
Abbreviation: N/A, not applicable.
– 28% had intensive care unit (ICU) admission, 13% had need for intervention, and 3.9% died
overall
– prognostic outcomes by severity using Atlanta reclassi cation (2012)
Outcome Mild Moderate Severe
ICU admission 3.2% 18.5% 84.6%

(p < 0.001 for all
pairwise
comparisons)
Need for 0% 12.3% 38.5%

intervention (p <
0.001 for all
pairwise
comparisons)
Mortality (p < 0% 0% 15.4%

0.001 for
moderate vs.
severe)
Abbreviation: ICU, intensive care unit.
– prognostic outcome by determinant-based classi cation
Outcome Mild Moderate Severe Critical

Outcome Mild Moderate Severe Critical
ICU 4.7% 42.1% 81.6% 88.2%

admission
(p < 0.001
for mild vs.
moderate
and
moderate
vs. severe)
Need for 0% 36.8% 22.5% 88.2%

intervention
(p < 0.001
for mild vs.
moderate
and severe
vs. critical)
Mortality 0% 0% 14.3% 17.7%

(no pairwise
comparison
s were
signi cant)
Abbreviation: ICU, intensive care unit.
– Atlanta reclassi cation (2012) and determinant-based classi cation had signi cantly better
prognostic performance compared to Atlanta classi cation system (1992) for prediction of ICU
admission and mortality in comparative analysis
– Reference - Am J Gastroenterol 2013 Dec;108(12):1911
STUDY
⚬ SUMMARY
computed tomography (CT) scoring systems do not appear superior to clinical scoring
systems for predicting severity of acute pancreatitis DynaMed Level 2
COHORT STUDY: Am J Gastroenterol 2012 Apr;107(4):612
Details
– based on retrospective cohort study without tests applied to all patients
– 346 consecutive patients with acute pancreatitis evaluated
– 150 patients (159 episodes) had abdominal CT scans within 24 hours of hospital admission and
were evaluated using 7 CT scoring systems and 2 clinical scoring systems
– CT scoring systems were
● CT severity index
● modi ed CT severity index
● pancreatic size index
● extrapancreatic score
● extrapancreatic in ammation on CT score
● mesenteric edema and peritoneal uid score
● Balthazar grade
– clinical scoring systems used
● Acute Physiology, Age, and Chronic Health Evaluation (APACHE II) score
● Bedside Index for Severity in Acute Pancreatitis (BISAP) score
– 18% had clinically severe acute pancreatitis, de ned as ≥ 1 of
● mortality
● persistent organ failure
● presence of local pancreatic complications requiring intervention
– mortality 6%
– no signi cant di erences in predictive performance for severe acute pancreatitis comparing CT
scoring systems and clinical scoring systems
– Reference - Am J Gastroenterol 2012 Apr;107(4):612
STUDY
● SUMMARY
combinations of existing prognostic scoring systems improve prediction of organ failure in
patients with acute pancreatitis but complexity may limit clinical use DynaMed Level 1
COHORT STUDY: Gastroenterology 2012 Jun;142(7):1476
Details
⚬ based on cohort study with independent derivation and validation cohorts
⚬ derivation cohort included 256 patients (mean age 51 years) with acute pancreatitis, and validation
cohort included 397 similar patients (mean age 52 years)
⚬ 9 clinical scores (APACHE-II, BISAP, Glasgow, HAPS, JSS, Panc 3, POP, Ranson, SIRS) were calculated
and blood urea nitrogen (BUN) and serum creatinine were measured at admission and at 48 hours
⚬ persistent organ failure de ned as cardiovascular, pulmonary, and/or renal failure for ≥ 48 hours
⚬ persistent organ failure developed in 24.2% of derivation cohort and 8.6% of validation cohort
⚬ range of negative predictive values was 93%-98% for each clinical score and biomarker
⚬ 12 predictive rules based on di erent combinations of scoring systems and biomarkers were
derived
⚬ combination rules had higher overall accuracy than individual scoring systems but were considered
impractical for clinical use
⚬ Reference - Gastroenterology 2012 Jun;142(7):1476
STUDY
● SUMMARY
3 risk scores have limited utility for prediction of invasive candidal infection in patients with
acute pancreatitis DynaMed Level 1
COHORT STUDY: Crit Care 2013 Mar 18;17(2):R49 | Full Text
Details
⚬ based on validation cohort study
⚬ 101 patients with severe acute pancreatitis admitted to intensive care unit and assessed with 3 risk
scores (Candida score, modi ed Invasive Candidiasis score, and Candida Colonization Index score)
for prediction of invasive candidal infection
⚬ 17.8% developed invasive candidal infection
⚬ all risk scores had low-to-moderate predictive performance for detection of candidal infection (c-
statistic range 0.59-0.79)
⚬ Reference - Crit Care 2013 Mar 18;17(2):R49 full-text
Other Prognostic Factors
STUDY
● SUMMARY
algorithm based on serial measurement of BUN predicts risk of in-hospital mortality in patients
with acute pancreatitis DynaMed Level 1
COHORT STUDY: Arch Intern Med 2011 Apr 11;171(7):669
Details
⚬ based on independent derivation and validation cohorts
⚬ 1,043 patients hospitalized with acute pancreatitis from 3 separate cohort studies were analyzed
⚬ all patients had BUN measurement at admission and at 24 hours
⚬ in pooled analysis of 3 cohorts, increased risk of in-hospital mortality associated with
– BUN ≥ 20 mg/dL at admission (odds ratio [OR] 4.6, 95% CI 2.5-8.3)

– any increase in BUN over 24 hours (OR 4.3, 95% CI 2.3-7.9)
⚬ algorithm to predict mortality derived in cohort of 521 patients
– if elevated BUN (≥ 20 mg/dL) at admission, decrease in BUN ≥ 5 mg/dL associated with reduced
risk of mortality
● mortality 2.9% in patients with decrease in BUN ≥ 5 mg/dL at 24 hours
● mortality 15% in patients with decrease in BUN < 5 mg/dL at 24 hours (p = 0.01)
– if normal BUN (< 20 mg/dL) at admission, increase in BUN ≥ 2 mg/dL associated with increased
risk of mortality
● mortality 0.9% in patients with increase in BUN < 2 mg/dL at 24 hours
● mortality 6.7% in patients with increase in BUN ≥ 2 mg/dL at 24 hours (p = 0 008)
⚬ algorithm validated in 2 additional cohorts
– in patients with elevated BUN at admission
● mortality 0%-3.3% in patients with BUN decrease ≥ 5 mg/dL at 24 hours

● mortality 9.1%-21% in patients with BUN decrease < 5 mg/dL at 24 hours
– in patients with normal BUN at admission
● mortality 0%-1% in patients with BUN increase < 2 mg/dL at 24 hours

● mortality 11%-15% in patients with BUN increase ≥ 2 mg/dL at 24 hours
⚬ Reference - Arch Intern Med 2011 Apr 11;171(7):669 , commentary can be found in Arch Intern
Med 2011 Apr 11;171(7):676
STUDY
● SUMMARY
obesity associated with increased severity and complications and nonsignificant increase in
mortality in patients with acute pancreatitis DynaMed Level 2
SYSTEMATIC REVIEW: Pancreatology 2006;6(3):206

Details
⚬ based on systematic review without assessment of study quality
⚬ systematic review of 5 studies evaluating 739 patients with acute pancreatitis
⚬ compared to patients without obesity, patients with obesity (de ned as body mass index ≥ 30
kg/m2) had increased risk for
– severe acute pancreatitis (pooled odds ratio [OR 2.9], 95% CI 1.8-4.6)
– systemic complications (OR 2.3, 95% CI 1.4-3.8)
– local complications (OR 3.8, 95% CI 2.4-6.6)
– mortality (OR 2.1, 95% CI 1-4.8)
⚬ Reference - Pancreatology 2006;6(3):206
STUDY
● SUMMARY
white blood cell count (WBC) and glucose level may predict complications and mortality in acute
alcoholic pancreatitis
COHORT STUDY: Arch Surg 2004 Sep;139(9):978
Details
⚬ 105 patients with rst admission for acute alcoholic pancreatitis evaluated
⚬ 26 patients (24.8%) had major systemic complication requiring intensive care unit admission and 6
patients (5.7%) died
⚬ for prediction of major complications
– serum glucose level 160 mg/dL or higher plus WBC 17,000 or more had 80% positive predictive
value
– admission Ranson score 3 or higher had 100% positive predictive value
⚬ for prediction of death
– WBC 17,000 or more had 99% negative predictive value (only 1% of patients with WBC < 17,000
died)
– admission Ranson score 1 or higher had 100% negative predictive value (no one with Ranson
score 0 died)
⚬ Reference - Arch Surg 2004 Sep;139(9):978
STUDY
● SUMMARY
elevated urinary trypsinogen activation peptide (TAP) may predict severe acute pancreatitis but
may not be superior to clinical scoring systems
COHORT STUDY: Lancet 2000 Jun 3;355(9219):1955
Details
⚬ 172 patients with acute pancreatitis (35 with severe disease) and 74 controls had tests of urinary
trypsinogen activation peptide (TAP) concentrations, plasma C-reactive protein and three
clinicobiochemical scoring systems at set times
⚬ at 24 hours after symptom onset
– urinary TAP > 35 nmol/L as predictor of severe vs. mild acute pancreatitis had 58% sensitivity,
73% speci city, 39% positive predictive value, and 86% negative predictive value
– C-reactive protein not useful for predicting severity of acute pancreatitis
⚬ at 48 hours after admission, for prediction of severe acute pancreatitis
Table 2. Results
APACHE Ranson Glasgow C- Urinary

II Score > Score > 3 Score > 3 reactive TAP > 25
8 Protein > nmol/L
150
mg/dL
Sensitivity 56% 89% 77% 86% 83%
Speci city 64% 64% 75% 61% 72%
Positive 30% 38% 44% 37% 44%

predictive
value
Negative 85% 96% 93% 94% 94%

predictive
value
Abbreviation: TAP, trypsinogen activation peptide.
– combined testing of C-reactive protein and TAP not superior to TAP alone
⚬ Reference - Lancet 2000 Jun 3;355(9219):1955 , editorial can be found in Lancet 2000 Jun
3;355(9219):1924 , commentary can be found in Lancet 2000 Aug 26;356(9231):766
STUDY
● SUMMARY
presence of several risk factors may predict need for surgery in patients with severe acute
pancreatitis managed by step-up approach
COHORT STUDY: Ann Surg 2013 Apr;257(4):737
Details
⚬ based on prospective cohort study
⚬ 70 patients with acute pancreatitis were managed using step-up approach
⚬ all patients initially received medical management, followed by image-guided ne-needle aspiration
and percutaneous catheter drainage, then open surgical necrosectomy if needed
– 14 were managed medically
– 29 were managed with percutaneous catheter drainage
– 27 required surgery
⚬ predictors of surgery include

– renal failure
– acute physiology and chronic health evaluation (APACHE) score > 7.5 at rst intervention
– number of bacteria isolated per patient
⚬ Reference - Ann Surg 2013 Apr;257(4):737
Prevention and Screening
Prevention
● prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis
⚬ to prevent severe post-ERCP pancreatitis in high-risk patients, use pancreatic duct stents and/or
postprocedure rectal nonsteroidal anti-in ammatory drug (NSAID) suppositories (ACG Conditional
⚬ guidewire-assisted cannulation during ERCP may decrease post-ERCP pancreatitis compared to
contrast-assisted cannulation (level 2 [mid-level] evidence )
⚬ medications
– prophylactic rectal indomethacin reduces risk and severity of post-ERCP pancreatitis (level 1
[likely reliable] evidence )
– rectal nonsteroidal anti-in ammatory drugs may be more e ective compared to pancreatic duct
stents for prevention of post-ERCP pancreatitis (level 2 [mid-level] evidence )
– octreotide ≥ 0.5 mg prevents post-ERCP pancreatitis (level 1 [likely reliable] evidence )
– prophylactic nitroglycerin may reduce incidence of post-ERCP pancreatitis (level 2 [mid-level]
evidence )
– corticosteroids do not prevent post-ERCP pancreatic injury (level 1 [likely reliable] evidence )
● treat very high triglyceride levels (> 1,000 mg/dL [11.3 mmol/L]) to prevent pancreatitis
⚬ treat with diet, physical exercise, and weight loss

⚬ medication options
– brates are drugs of choice to reduce risk for pancreatitis (Endocrine Society Strong
– niacin or omega-3 fatty acids may also be considered
– statins not recommended as rst-line therapy or as monotherapy (Endocrine Society Strong
recommendation, Low-quality evidence)
– bile acid sequestrants contraindicated (may raise triglycerides)
– if hyperglycemia, start or increase glucose-lowering drugs
● prevention of recurrence of gallstone-related pancreatitis
⚬ perform cholecystectomy in patients with mild acute pancreatitis and gallstones in gallbladder
before discharge to prevent recurrence of acute pancreatitis (ACG Strong recommendation,
Moderate-quality evidence)
⚬ to prevent infection in patients with necrotizing biliary acute pancreatitis, defer cholecystectomy
until active in ammation subsides and uid collections resolve or stabilize (ACG Strong
● treat alcohol abuse disorders to decrease risk of recurrence of alcohol-related acute pancreatitis
● see Prevention of Acute Pancreatitis for details

Screening
● not applicable
Quality Improvement
Choosing Wisely
● American Society for Clinical Pathology recommends against testing for amylase in cases of suspected
acute pancreatitis, instead, test for lipase (Choosing Wisely 2016 Sept 16)
Guidelines and Resources
Guidelines
International guidelines
● World Congress of Emergency Surgery guidelines for the management of severe acute pancreatitis
can be found in World J Emerg Surg 2019;14:27 full-text
● International Association of Pancreatology/American Pancreatic Association (IAP/APA) evidence-based

guideline on management of acute pancreatitis can be found in Pancreatology 2013 Jul-Aug;13(4
Suppl 2):e1 full-text
● International Association of Pancreatology (IAP) guideline on diagnostic criteria for autoimmune

pancreatitis can be found in Pancreas 2011 Apr;40(3):352
● International Association of Pancreatology (IAP) consensus on treatment of autoimmune pancreatitis

can be found in Pancreatology 2017 Jan - Feb;17(1):1
● International Consensus Guideline Committee Pancreatitis Task Force consensus guideline on

nutrition therapy in pancreatitis can be found in JPEN J Parenter Enteral Nutr 2012 May;36(3):284
● Acute Pancreatitis Working Group international consensus on classi cation of acute pancreatitis: 2012
revision of Atlanta classi cation and de nitions can be found in Gut 2013 Jan;62(1):102
● European Society for Pediatric Gastroenterology, Hepatology and Nutrition/North American Society
for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN/NASPGHAN) position paper on
nutritional considerations in pediatric pancreatitis can be found in J Pediatr Gastroenterol Nutr 2018
Jul;67(1):131 PDF
United States guidelines
● American Gastroenterological Association (AGA) Institute guideline on initial management of acute

pancreatitis can be found in Gastroenterology 2018 Mar;154(4):1096 , commentary can be found in
Gastroenterology 2018 Jul;155(1):234
● American Gastroenterological Association (AGA) Institute clinical practice update on management of

pancreatic necrosis can be found in Gastroenterology 2020 Jan;158(1):67
● American College of Gastroenterology (ACG) guideline on management of acute pancreatitis can be

found at or in Am J Gastroenterol 2013 Sep;108(9):1400 PDF
● North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) clinical
report on classi cation of acute pancreatitis in pediatric patients can be found in J Pediatr
Gastroenterol Nutr 2017 Jun;64(6):984 PDF
● American College of Radiology (ACR) Appropriateness Criteria for acute pancreatitis can be found at
ACR 2013 PDF or in Ultrasound Q 2014 Dec;30(4):267
● Eastern Association for the Surgery of Trauma (EAST) guideline on surgical management of pancreatic
necrosis can be found at EAST 2017 or in J Trauma Acute Care Surg 2017 Aug;83(2):316
● University of Michigan Health System (UMHS) guideline on evaluation and management of gallstone-
related diseases in nonpregnant adults can be found at UMHS 2014 May PDF
● American Society for Gastrointestinal Endoscopy (ASGE)
⚬ ASGE quality indicators for endoscopic retrograde cholangiopancreatography (ERCP) can be found
in Gastrointest Endosc 2015 Jan;81(1):54 PDF , correction can be found in Gastrointest Endosc
2015 Apr;81(4):1060
⚬ ASGE guideline on adverse events associated with ERCP can be found in Gastrointest Endosc 2017
Jan;85(1):32 PDF
● Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guideline on clinical

application of laparoscopic biliary tract surgery can be found in Surg Endosc 2010 Oct;24(10):2368
● Academy of Nutrition and Dietetics (AND) evidence-based nutrition practice guideline on critical illness
can be found at AND Evidence Analysis Library 2012 Sep
● American Society for Apheresis (ASFA) guideline on the use of therapeutic apheresis in clinical practice
can be found in J Clin Apher 2019 Jun;34(3):171
United Kingdom guidelines
● National Institute for Health and Care Excellence (NICE) guideline on pancreatitis can be found at NICE
2018 Sept:NG104 PDF
European guidelines
● S3 Leitlinie Klinische Ernährung in der Gastroenterologie (Teil 2) – Pankreas nden Sie unter AWMF
2014 PDF [Deutsch]
● Italian Association for the Study of the Pancreas (AISP) consensus guideline on severe acute
pancreatitis can be found in Dig Liver Dis 2015 Jul;47(7):532 PDF
● Catalan Society of Gastroenterology/Catalan Society of Surgery/Catalan Society of the Pancreas

(Societat Catalana de Digestologia/Societat Catalana de Cirurgia/Societat Catalana de Pàncrees
[SCD/SC Cirurgia/SCPanc) position document on assessment and treatment of acute pancreatitis can
be found at SCD 2014 PDF or in Gastroenterol Hepatol 2015 Feb;38(2):82 [Spanish]
● Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC)
⚬ SEMICYUC guideline on clinical pathways in acute pancreatitis: recommendations for early

multidisciplinary management can be found in Med Intensiva 2012 Jun-Jul;36(5):351 full-text
[English, Spanish]
⚬ SEMICYUC consensus recommendations on intensive care management of acute pancreatitis can
be found in Med Intensiva 2013 Apr;37(3):163 full-text , correction can be found in Med
Intensiva 2014 Mar;38(2):131 [English, Spanish]
● Hungarian Pancreatic Study Group evidence-based practice guideline on acute pancreatitis can be
found in Orv Hetil 2015 Feb 15;156(7):244 [Hungarian]
● European Society of Gastrointestinal Endoscopy (ESGE) guidelines on
⚬ endoscopic management of acute necrotizing pancreatitis can be found in Endoscopy 2018

May;50(5):524 full-text
⚬ prophylaxis of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis can be
found in Endoscopy 2014 Sep;46(9):799 PDF
● Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) S3 guideline

on sedation in gastrointestinal endoscopy can be found at AWMF 2014 PDF [German]
● Romanian Association for Pancreatic Pathology (APPR) guideline on diagnosis and treatment of
exocrine pancreatic insu ciency can be found in J Gastrointestin Liver Dis 2015 Mar;24(1):117 PDF
Asian guidelines
● Japan Pancreas Society (JPS)
⚬ JPS clinical practice guideline on management of acute pancreatitis can be found at JPS 2015 PDF
[Japanese 日本語] or in J Hepatobiliary Pancreat Sci 2015 Jun;22(6):405 full-text [English],
mobile application download including calculators of diagnostic criteria and severity assessment
can be found at JSHBPS 2015
⚬ JPS guideline on post-ERCP pancreatitis can be found at Minds guideline listing (医療情報サービスマ
インズ) PDF [Japanese 日本語]
● Asian Endoscopic Ultrasonography (EUS) group guidelines on optimal management of interventional

EUS procedures can be found in Gut 2018 Jul;67(7):1209
Mexican guidelines
● Grupos de Desarrollo de las Instituciones Públicas del Sistema Nacional de Salud de México
(Secretaría de Salud, IMSS, ISSSTE, SEDENA, SEMAR, DIF, PEMEX) guías de práctica clínica en
⚬ diagnóstico y tratamiento de la pancreatitis aguda se pueden encontrar en Secretaría de Salud-
México 2015 PDF [Spanish]
⚬ diagnóstico y referencia oportuna de la pancreatitis aguda en el primer nivel de atención se
pueden encontrar en Secretaría de Salud-México 2012 PDF [Spanish]
Review articles
● review can be found in Lancet 2020 Sep 5;396(10252):726
● review can be found in Nat Rev Gastroenterol Hepatol 2019 Aug;16(8):479
● review can be found in J Emerg Med 2018 Dec;55(6):769

● review can be found in F1000Res 2018;7:doi: 10.12688/f1000research.14244.2) full-text
● review can be found in N Engl J Med 2016 Nov 17;375(20):1972
● review can be found in Lancet 2015 Jul 4;386(9988):85
● review can be found in Am Fam Physician 2014 Nov 1;90(9):632
● review can be found in BMJ 2014 Aug 12;349:g4859
● review of management of acute pancreatitis can be found in Frontline Gastroenterol 2019

Jul;10(3):292
● review of management of severe acute pancreatitis can be found in BMJ 2019 Dec 2;367:l6227
● review of endoscopic retrograde cholangiopancreatography for gallstone pancreatitis can be found in

N Engl J Med 2014 Jan 9;370(2):150 , correction can be found in N Engl J Med 2014 Jan 30;370(5):488
● review of endoscopic transmural drainage for necrotizing pancreatitis can be found in Am J

Gastroenterol 2014 Jul;109(7):969
● review of exocrine pancreatic function can be found in J Pediatr Gastroenterol Nutr 2015 Jul;61(1):144
● review of interventional radiology for necrotizing pancreatitis can be found in J Gastrointest Surg 2011
Jul;15(7):1101
● review of endoscopic pancreatic necrosectomy can be found in J Gastrointest Surg 2011 Jul;15(7):1098
● case reports
⚬ case presentation of recurrent acute pancreatitis due to genetic abnormality can be found in N
Engl J Med 2011 Oct 20;365(16):1528 , commentary can be found in N Engl J Med 2012 Feb
16;366(7):669
⚬ case report of hyperlipidemia-associated pancreatitis in pregnancy managed with feno brate can
be found in Obstet Gynecol 2011 Feb;117(2 Pt 2):517
MEDLINE search
● to search MEDLINE for (Acute pancreatitis) with targeted search (Clinical Queries), click therapy ,
diagnosis , or prognosis
Patient Information
● handouts from
⚬ acute pancreatitis in adults or in Spanish

⚬ acute pancreatitis in children or in Spanish
● handout from Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) in English PDF
or in German PDF
● handout from Patient UK PDF
● handout on pancreatitis from American Academy of Family Physicians or in Spanish
● information on managing the intensive care unit experience from American Thoracic Society PDF
ICD Codes
ICD-10 Codes
● K85 acute pancreatitis
⚬ K85.0 idiopathic acute pancreatitis

⚬ K85.1 biliary acute pancreatitis
⚬ K85.2 alcohol-induced acute pancreatitis
⚬ K85.3 drug-induced acute pancreatitis
– use additional external cause code (Chapter XX ), if desired, to identify drug

⚬ K85.8 other acute pancreatitis
⚬ K85.9 acute pancreatitis, unspeci ed
References
General References Used
1. Tenner S, Baillie J, DeWitt J, Vege SS; American College of Gastroenterology. American College of
Gastroenterology guideline: management of acute pancreatitis. Am J Gastroenterol. 2013
Sep;108(9):1400-15 PDF
2. Banks PA, Bollen TL, Dervenis C, et al; Acute Pancreatitis Classi cation Working Group. Classi cation of
acute pancreatitis--2012: revision of the Atlanta classi cation and de nitions by international
consensus. Gut. 2013 Jan;62(1):102-11
3. Forsmark CE, Vege SS, Wilcox CM. Acute Pancreatitis. N Engl J Med. 2016 Nov 17;375(20):1972-1981
4. Crockett SD, Wani S, Gardner TB, Falck-Ytter Y, Barkun AN, American Gastroenterological Association
Institute Clinical Guidelines Committee. American Gastroenterological Association Institute Guideline
on Initial Management of Acute Pancreatitis. Gastroenterology. 2018 Mar;154(4):1096-1101
5. American Gastroenterological Association (AGA) Institute on "Management of Acute Pancreatitis"

Clinical Practice and Economics Committee, AGA Institute Governing Board. AGA Institute medical
position statement on acute pancreatitis. Gastroenterology. 2007 May;132(5):2019-21 , supporting
literature review in Gastroenterology 2007 May;132(5):2022
6. Quinlan JD. Acute pancreatitis. Am Fam Physician. 2014 Nov 1;90(9):632-9 full-text
Recommendation Grading Systems Used

● Endocrine Society uses Grading of Recommendations, Assessment, Development, and Evaluation
(GRADE) system
⚬ strength of recommendation
– Strong recommendation - guideline panel members have high con dence that desirable e ects
of recommendation outweigh undesirable e ects (or vice versa)
– Weak recommendation - guideline panel members conclude with less con dence that desirable
e ects of recommendation probably outweigh undesirable e ects, or bene ts and harms are
nely balanced, or appreciable uncertainty
⚬ quality of evidence
– High-quality evidence - consistent evidence from well-performed randomized controlled trials,

or exceptionally strong evidence from unbiased observational studies
– Moderate-quality evidence - randomized controlled trials with important limitations
(inconsistent results, methodological aws, indirect or imprecise evidence), or unusually strong
evidence from unbiased observational studies
– Low-quality evidence - ≥ 1 critical outcome from observational studies, randomized controlled
trials with serious aws, or indirect evidence
– Very low-quality evidence - ≥ 1 of the critical outcomes from unsystematic clinical observations
or very indirect evidence
⚬ Reference - Endocrine Society clinical practice guideline on evaluation and treatment of
hypertriglyceridemia (J Clin Endocrinol Metab 2012 Sep;97(9):2969 )
● American College of Gastroenterology (ACG) uses Grading of Recommendations Assessment,

Development and Evaluation (GRADE) system
– Strong recommendation - high quality evidence to support a recommendation for or against

use and/or bene ts of use clearly outweigh adverse e ects
– Conditional (weak) recommendation - low quality evidence to support a recommendation for or
against use and/or bene ts of use do not clearly outweigh adverse e ects
– High-quality evidence - further research very unlikely to change con dence in estimate of e ect
– Moderate-quality evidence - further research likely to have important impact on con dence in
estimate of e ect and may change estimate
– Low-quality evidence - further research very likely to have important impact on con dence in
estimate of e ect and is likely to change estimate
– Very low-quality evidence - any estimate of e ect is very uncertain
⚬ Reference - ACG guideline on management of acute pancreatitis (Am J Gastroenterol 2013

Sep;108(9):1400 PDF )
● Infectious Disease Society of America (IDSA) strength of recommendation and quality evidence grades
⚬ strength of recommendations
– Grade A - good evidence to support a recommendation for or against use

– Grade B - moderate evidence to support a recommendation for or against use
– Grade C - poor evidence to support a recommendation
– Level I - evidence from > 1 properly randomized, controlled trial

– Level II - evidence from > 1 well-designed clinical trial, without randomization; from cohort or
case-controlled analytic studies (preferably from > 1 center); from multiple time series; or from
dramatic results from uncontrolled experiments
– Level III - evidence from opinions of authorities, based on clinical experience, descriptive
studies, or reports of expert committees
⚬ Reference - IDSA guideline on diagnosis and management of complicated intra-abdominal
infection in adults and children (Surg Infect (Larchmt) 2010 Feb;11(1):79 PDF )
● American Society for Apheresis (ASFA) recommendation grading system
⚬ categories of indications for therapeutic apheresis
– Category I - disorders for which apheresis is accepted as rst-line therapy, either as primary
stand-alone treatment or in conjunction with other modes of treatment
– Category II - disorders for which apheresis is accepted as second-line therapy, either as stand-
alone treatment or in conjunction with other modes of treatment
– Category III - optimum role of apheresis therapy is not established and decision-making should
be individualized
– Category IV - disorders in which published evidence demonstrates or suggests apheresis to be
ine ective or harmful; Institutional Review Board (IRB) approval is desirable if apheresis
treatment is undertaken in these circumstances
⚬ grades of recommendations
– Grade 1A - strong recommendation, high-quality evidence
● can apply to most patients in most circumstances without reservation

● supported by randomized controlled trials (RCTs) without important limitations or
overwhelming evidence from observational studies
– Grade 1B - strong recommendation, moderate-quality evidence
● can apply to most patients in most circumstances without reservation

● supported by RCTs with important limitations (inconsistent results, methodological aws,
indirect, or imprecise) or exceptionally strong evidence from observational studies
– Grade 1C - strong recommendation, low- or very low-quality evidence
● recommendation may change when higher quality evidence becomes available

● supported by observational studies or case series
– Grade 2A - weak recommendation, high-quality evidence
● best action may di er depending on circumstances of patients' or societal values

● supported by RCTs without important limitations or overwhelming evidence from
observational studies
– Grade 2B - weak recommendation, moderate-quality evidence
● best action may di er depending on circumstances of patients' or societal values

● supported by RCTs with important limitations (inconsistent results, methodological aws,
indirect, or imprecise) or exceptionally strong evidence from observational studies
– Grade 2C - weak recommendation, low- or very low-quality evidence
● very weak recommendation; other alternatives may be equally reasonable

● supported by observational studies or case series
⚬ Reference - ASFA guideline on use of therapeutic apheresis in clinical practice (J Clin Apher 2019
Jun;34(3):171 )
● European Association for the Study of the Liver (EASL) grading of recommendations
⚬ strength of recommendations
– Strong recommendation - most or all individuals in relevant population will bene t by following
recommendation; there is certainty about various factors including aggregate evidence quality
and assessment of anticipated bene ts and harms
– Weak recommendation - there is uncertainty about various factors including aggregate
evidence quality and assessment of anticipated bene ts and harms
⚬ quality of evidence grades
– High-quality evidence - further research very unlikely to change con dence in estimate of e ect;
randomized trials or double-upgraded observational studies
– Moderate-quality evidence - further research likely to have important impact on con dence in
estimate of e ect and may change estimate; downgraded randomized trials or upgraded
observational studies
– Low-quality evidence - further research very likely to have important impact on con dence in
estimate of e ect and likely to change estimate; observational studies or double-downgraded
randomized trials
– Very low-quality evidence - estimate is very uncertain; case series/case reports, downgraded
observational studies, triple-downgraded randomized trials
⚬ Reference - EASL clinical practice guideline on prevention, diagnosis, and treatment of gallstones (J
Hepatol 2016 Jul;65(1):146 )
● American Gastroenterological Association (AGA) uses Grade of Recommendations Assessment,

Development and Evaluation (GRADE) system
– Strong -most individuals should receive the recommended course of action. Formal decision
aids are not likely to be needed to help individuals make decisions consistent with their values
and preferences
– Conditional - di erent choices will be appropriate for di erent patients. Decision aids may be
useful in helping individuals in making decisions consistent with their values and preferences.
Clinicians should expect to spend more time with patients when working toward a decision
– No recommendation - con dence in e ect estimate is so low that any recommendation is
speculative at this time
– High - very con dent that the true e ect lies close to estimate of e ect
– Moderate - moderately con dent in estimate of e ect; the true e ect is likely to be close to
estimate of e ect, but there is a possibility that it is substantially di erent
– Low - con dence in the e ect estimate is limited; the true e ect may be substantially di erent
from the estimate of e ect
– Very low - very little con dence in e ect estimate; the true e ect is likely to be substantially
di erent from estimate of e ect
⚬ Reference - AGA guideline on initial management of acute pancreatitis (Gastroenterology 2018
Mar;154(4):1096 )
● International Association of Pancreatology/American Pancreatic Association (IAP/APA) uses modi ed

Grading of Recommendations Assessment, Development and Evaluation (GRADE) system
– 1 (Strong) - desirable e ects of an intervention clearly outweigh the undesirable e ects, or

clearly do not
– 2 (Weak) - trade-o s are less certain, either because of low quality evidence or because
evidence suggests that desirable and undesirable e ects are closely balanced
⚬ levels of evidence
– A (High) - Further research is very unlikely to change con dence in estimate of e ect
– B (Moderate) - Further research is likely to have an important impact on con dence in estimate
of e ect and may change estimate
– C (Low) - Further research is very likely to have an important impact on con dence in estimate
of e ect and is likely to change estimate
⚬ Agreement - strength of agreement (strong/weak) determined by plenary voting using ve point
Likert scale
⚬ Reference - IAP/APA evidence-based guidelines for the management of acute pancreatitis
(Pancreatology 2013 Jul;13(4 Suppl 2):e1 )
● American College of Radiology (ACR) grading system
⚬ 7, 8, or 9 (Usually Appropriate) - imaging procedure or treatment is indicated in the speci ed

clinical scenarios at a favorable risk-bene t ratio for patients
⚬ 4, 5, or 6 (May be Appropriate) - imaging procedure or treatment may be indicated in the speci ed
clinical scenarios as an alternative to imaging procedures or treatments with a more favorable risk-
bene t ratio, or the risk-bene t ratio for patients is equivocal
⚬ 4, 5, or 6 (May be Appropriate - Disagreement) - individual ratings are too dispersed from the panel
median; di erent label provides transparency regarding the panel’s recommendation. “May be
appropriate” is the rating category and a rating of 5 is assigned
⚬ 1, 2, or 3 (Usually Not Appropriate) - imaging procedure or treatment is unlikely to be indicated in
the speci ed clinical scenarios, or the risk-bene t ratio for patients is likely to be unfavorable
⚬ Reference - ACR appropriateness criteria for acute pancreatitis (J Am Coll Radiol 2019
Nov;16(11S):S316 )
Synthesized Recommendation Grading System for DynaMed Content
● The DynaMed Team systematically monitors clinical evidence to continuously provide a synthesis of
the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based
Methodology ).
● Guideline recommendations summarized in the body of a DynaMed topic are provided with the
recommendation grading system used in the original guideline(s), and allow users to quickly see
where guidelines agree and where guidelines di er from each other and from the current evidence.
● In DynaMed content, we synthesize the current evidence, current guidelines from leading authorities,
and clinical expertise to provide recommendations to support clinical decision-making in the Overview
& Recommendations section.
● We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to

classify synthesized recommendations as Strong or Weak.
⚬ Strong recommendations are used when, based on the available evidence, clinicians (without
con icts of interest) consistently have a high degree of con dence that the desirable consequences
(health bene ts, decreased costs and burdens) outweigh the undesirable consequences (harms,
costs, burdens).
⚬ Weak recommendations are used when, based on the available evidence, clinicians believe that
desirable and undesirable consequences are nely balanced, or appreciable uncertainty exists
about the magnitude of expected consequences (bene ts and harms). Weak recommendations are
used when clinicians disagree in judgments of relative bene t and harm, or have limited
con dence in their judgments. Weak recommendations are also used when the range of patient
values and preferences suggests that informed patients are likely to make di erent choices.
● DynaMed synthesized recommendations (in the Overview & Recommendations section) are
determined with a systematic methodology:
⚬ Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological
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⚬ Recommendations are phrased to match the strength of recommendation. Strong
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recommended action for most patients. Weak recommendations use "consider" or "suggested"
phrasing.
⚬ Recommendations are explicitly labeled as Strong recommendations or Weak
recommendations when a quali ed group has explicitly deliberated on making such a
recommendation. Group deliberation may occur during guideline development. When group
deliberation occurs through DynaMed Team-initiated groups:
– Clinical questions will be formulated using the PICO (Population, Intervention, Comparison,
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– All recommendation panel members must disclose any potential con icts of interest
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– Panel members will make Strong recommendations if and only if there is consistent
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Special Acknowledgements
●
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Acute Pancreatitis in Adults

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Acute Pancreatitis in Adults

Overview and Recommendations

● Severity can be assessed according to the revised Atlanta criteria.

⚬ Revised Atlanta criteria assess the following factors:

– local complications such as pseudocyst, pancreatic necrosis.

⚬ Moderately severe acute pancreatitis is de ned as nding of complications, such as:

– peripancreatic uid collection or peripancreatic necrosis

● Establishing a diagnosis of acute pancreatitis:

⚬ Typical features of acute pancreatitis include:

– acute epigastric or left upper quadrant abdominal pain

⚬ Obtain serum amylase and lipase if acute pancreatitis is suspected.

– abdominal pain consistent with pancreatitis

● Perform endoscopic retrograde cholangiopancreatography (ERCP) within 24 hours if there is

● Ensure adequate nutrition.

● In severe acute pancreatitis:

● Do not perform drainage or debridement for asymptomatic pancreatic pseudocysts or necrosis

● if infected necrosis is suspected, obtain a computed tomography (CT)-guided ne-needle aspiration

● In patients with gallstones, perform cholecystectomy (Strong recommendation).

⚬ In mild cases, perform before discharge.

● Acute Pancreatitis in Children

● Prevention of Acute Pancreatitis

● Causes of Acute Pancreatitis

Hospitalist Focused Content

● Dr. Duggirala declares no relevant nancial con icts of interest.

● Dr. Huang declares no relevant nancial con icts of interest.

● Dr. Rothman declares no relevant nancial con icts of interest.

● Dr. Solorza declares no relevant nancial con icts of interest.

● Dr. Tarragona declares no relevant nancial con icts of interest.

● Dr. Quintana-Garcia declares no relevant nancial con icts of interest.

General Admission Checklist

● Determine code status Consensus

● Determine appropriate treatment settingConsensus

● Diet should be nothing per mouth (NPO) on admissionConsensus

⚬ Outpatient advanced directives

Admission Checklist for Patients With Acute Pancreatitis

● Obtain imaging if diagnosis is unclear, otherwise computed tomography, magnetic resonance

Conditional recommendation, Moderate-quality evidence) 1

nutrition recommended (AGA Strong recommendation, Moderate-quality evidence) 4

● Patients with obesity

● Patients needing large volume of resuscitation

● Patients with pancreatic necrosis

● Reference - Lancet 2008 Jan 12;371(9607):143

Admission to ICU also indicated if severe disease, including presence of: 1 , 3 , 5 , 6

● Signi cant gastrointestinal bleeding

● Features of substantial third-space loss (hypotension, tachycardia, azotemia, or signi cant

● Evidence of systemic in ammatory response syndrome (SIRS)

Consultation and Referral

Interventional radiology assistance may be indicated for management or sampling of pancreatic

Consider endocrinology consultation in patients with hypertriglyceridemia-induced pancreatitis for

Consider consultation with pheresis team for hypertriglyceridemia (institution-dependent).Consensus

Social work or other psychological counseling for alcohol-induced pancreatitis. 5

Start discharge planning on day one. (J Hosp Med 2013 Aug;8(8):421 )

Discontinue any medication implicated in causation of pancreatitis when possible.Consensus

Ensure diet or stable enteral nutrition is well tolerated.Consensus

General Discharge Checklist

● Ensure communication with outpatient providers about hospital courseConsensus

Discharge Checklist for Patients With Acute Pancreatitis

● Consider dietitian consultation for low-fat diet to be maintained during convalescenceConsensus

● Referral for cholecystectomy if gallstones present and unable to perform in-hospital 1

● Ensure close primary care follow-up within 1 week of dischargeConsensus

● Communicate any pending workup for etiology with following providersConsensus

● Referral to alcohol cessation resources as appropriate 3 , 5

● Counsel to stop smoking if applicable and provide resources to do so 3 , 5

or systemic complications and organ failure 4