Annals of Internal MedicineT

In the ClinicT

Acute Pancreatitis
Prevention

A
cute pancreatitis is one of the most com-
mon reasons for gastroenterology-related
hospitalization in the United States. With
significant morbidity and subsequent mortality Diagnosis
related to both the acute presentation and subse-
quent sequelae, prompt diagnosis and appropriate
management are critical, especially in the first 24 Treatment
hours of illness. It is also important to accurately
recognize complications, such as pancreatic fluid
collections and vascular events, and identify a de- Practice Improvement
finitive cause so that a strategy to prevent future
attacks can be implemented.

CME/MOC activity available at Annals.org.

Physician Writer doi:10.7326/AITC202102160

Timothy B. Gardner, MD, MS
Dartmouth–Hitchcock Medical
Center, Hanover, New
Hampshire
This article was published at Annals.org on 9 February 2021.
CME Objective: To review current evidence for prevention, diagnosis, treatment,
and practice improvement of acute pancreatitis.
Funding Source: American College of Physicians.
Acknowledgment: The author thanks Kapil Gupta, MD, MPH, and Bechien Wu,
MD, MPH, authors of the previous version of this In the Clinic.
Disclosures: Dr. Gardner, ACP Contributing Author, has nothing to disclose. The
form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms
.do?msNum=M20-5976.

With the assistance of additional physician writers, the editors of Annals of

Internal Medicine develop In the Clinic using MKSAP and other resources of
the American College of Physicians. The patient information page was written by
Monica Lizarraga from the Patient and Interprofessional Partnership Initiative at
the American College of Physicians.
In the Clinic does not necessarily represent official ACP clinical policy. For ACP
clinical guidelines, please go to https://www.acponline.org/clinical_information
/guidelines/.
© 2021 American College of Physicians

1. Banks PA, Bollen TL,
Dervenis C, et al; Acute
Pancreatitis Classification
Working Group. Classifica-
tion of acute pancreatitis—
2012: revision of the
Atlanta classification and
definitions by international
consensus. Gut. 2013;
62:102-11. [PMID:
23100216] doi:10.1136
/gutjnl-2012-302779
2. Gapp J, Hall AG, Walters
RW. Trends and outcomes
of hospitalizations related
to acute pancreatitis: epide-
miology from 2001 to
2014 in the United States.
Pancreas. 2019;48:548-54.
[PMID: 30946239]
doi:10.1097/MPA
.0000000000001275
3. Peery AF, Crockett SD,
Murphy CC. Burden and
cost of gastrointestinal,
liver, and pancreatic dis-
eases in the United States:
update 2018. Gastro-enter-
ology. 2019;156:254-272.
e11. [PMID: 30315778]
doi:10.1053/j.gastro
.2018.08.063
4. Lankisch PG, Breuer N,
Bruns A. Natural history of
acute pancreatitis: a long-
term population-based
study. Am J Gastroenterol.
2009;104:2797-805.
[PMID: 19603011]
doi:10.1038/ajg.2009.405
5. Vege SS, DiMagno MJ,
Forsmark CE. Initial medical
treatment of acute pancrea-
titis: American Gastro-
enterological Association
Institute technical review.
Gastroenterology. 2018;
154:1103-39. [PMID:
29421596] doi:10.1053/j.
gastro.2018.01.031
6. Miquel JF, Rollan A,
Guzman S. Microlithiasis
and cholesterolosis in ‘idio-
pathic’ acute pancreatitis
[Letter]. Gastroenterology.
1992;102:2188-90. [PMID:
1587452]
7. Yadav D. The role of alcohol
and smoking in pancreati-
tis. Nat Rev Gastroenterol
Hepatol. 2010;7:131-45.
[PMID: 20125091]
doi:10.1038/nrgastro
.2010.6
8. Kristiansen L, Grønbaek M,
Becker U. Risk of pancreati-
tis according to alcohol
drinking habits: a popula-
tion-based cohort study.
Am J Epidemiol. 2008;
168:932-7. [PMID:
18779386] doi:10.1093/
aje/kwn222
9. Yang AL. Hypertriglyceri-
demia and acute pancreati-
tis. Pancreatology. 2020;
20:795-800. [PMID:
32571534] doi:10.1016/j.
pan.2020.06.005
10. Yadav D. Issues in hyper-
lipidemic pancreatitis. J
Clin Gastroenterol.
2003;36:54-62. [PMID:
12488710]
© 2021 American College of Physicians
Acute pancreatitis is an acute
inflammatory process of the pan-
creas that can occur as an isolated
event or be due to relapsing epi-
sodes (recurrent acute pancreatitis).
Acute pancreatitis is a heterogene-
ous disease ranging from the mini-
mal inflammation seen in mild
interstitial pancreatitis to the exten-
sive pancreatic necrosis and multi-
system organ failure of severe
attacks. Diagnosis is based on the
presence of at least 2 of 3 features:
characteristic abdominal pain,
increased pancreatic enzyme levels
(amylase and/or lipase) to 3 or
more times the upper limit of nor-
mal, or imaging tests showing char-
acteristic findings (1). Excessive
Prevention
What are the risk factors for
acute pancreatitis?
The most common causes of acute
pancreatitis are gallstone disease
(approximately 35% to 40% of
cases) and excessive alcohol con-
sumption (approximately 30% of
cases) (Table 1) (5). Gallstone dis-
ease is among the most common
disorders in the United States and
can present in acute pancreatitis as
a discrete stone, sludge, or micro-
scopic crystals (microlithiasis) (6). It
is difficult to predict which patients
with symptomatic or asymptomatic
gallstones or microlithiasis will de-
velop pancreatitis. One risk factor is
the presence of stones in the com-
mon bile duct (choledocholithiasis),
especially stones less than 2 mm in
diameter (microlithiasis), because
they can obstruct the orifice of the
pancreatic duct at the level of the
ampulla. The exact mechanisms by
which pancreatitis is caused by
stones or microlithiasis in the com-
mon bile duct are controversial.
One theory is that obstruction of
the stone at the sphincter of Oddi
blocks the flow of pancreatic fluid
containing digestive enzymes into
the duodenum, thereby leading to
activated enzymes in the pancreas
ITC18 In the Clinic
alcohol consumption and gall-
stones are the 2 most common
causes, but there are many less
common causes. Acute pancreatitis
accounts for almost 300 000 hospi-
talizations annually in the United
States, and from 2001 to 2014, the
rate of it being the primary dis-
charge diagnosis increased from
65.38 to 81.88 per 100 000 adults
per year (2). It is also very costly, with
an estimated total cost for acute
pancreatitis admissions in the United
States of $2.64 billion in 2014 (3).
Mortality from acute pancreatitis is
less than 5% overall, but severe and
moderately severe attacks require
longer hospitalization and can lead to
higher mortality (4).
and subsequent severe inflamma-
tion. Another theory is that obstruc-
tion of the stone at the ampulla
leads to reflux of bile into the pan-
creatic duct, thereby triggering the
cascade of intrapancreatic enzyme
activation. To reduce risk for pan-
creatitis, patients with symptomatic
gallstones usually should undergo
cholecystectomy, and those with
common bile duct stones, even if
asymptomatic, should have them
removed by endoscopic retro-
grade cholangiopancreatography
(ERCP), an imaging and therapeutic
technique that combines endos-
copy and fluoroscopy. Medical dis-
solution therapy, such as using
ursodeoxycholic acid, has not been
shown to prevent pancreatitis.
Alcohol-related pancreatitis usually
occurs after long-term (>10 years),
heavy alcohol consumption. Risk
increases with the amount con-
sumed, indicating a direct toxic
effect on the pancreas when the
alcohol is metabolized. Because
only about 5% of persons with alco-
hol use disorder develop pancreati-
tis, additional unknown genetic or
other factors likely increase suscep-
tibility; for example, smoking
tobacco has been reported to
Annals of Internal Medicine February 2021
accelerate progression of estab-
lished alcoholic pancreatitis (7). The
amount of daily alcohol intake
required to cause pancreatitis is not
known. One study found an associ-
ation with high intake of beer (>14
drinks per week) but no association
for wine or spirits (8).
Hypertriglyceridemia is another
important risk factor for pancreati-
tis and is commonly cited as hav-
ing the highest risk for progression
to a severe attack (9). No clear risk
profile can indicate which patients
with elevated triglycerides will de-
velop pancreatitis, but it is rare in
the absence of significant eleva-
tions (usually >1000 mg/dL) (10).
Several drugs have been linked to
acute pancreatitis (Table 1), but
Table 1. Causes of Acute Pancreatitis
Cause
More common
Gallstones and microlithiasis
Alcohol misuse
Drugs
ERCP
Hyperlipidemia
Hypercalcemia
Genetic
Type 2 autoimmune pancreatitis
Infection
Cystic lesions of the pancreas
Idiopathic
Less common
Pancreas divisum
Pancreatic cancer
Penetrating peptic ulcer
Postsurgical
Trauma
Tropical pancreatitis
Vasculitis
Scorpion bite
ERCP = endoscopic retrograde cholangiopancreatography.
February 2021 Annals of Internal Medicine
the risk is generally low. In one
review, the authors assessed the
evidence for specific drugs caus-
ing acute pancreatitis as well as
their clinical presentations and
proposed a classification of drug-
induced pancreatitis (11). Patients 11. Badalov N, Baradarian
R, Iswara K. Drug-
who develop apparent drug- induced acute pancreati-
induced acute pancreatitis should tis: an evidence-based
review. Clin Gastro-
still be evaluated for other causes enterol Hepatol.
before an episode is attributed to 2007;5:648-61. [PMID:
17395548]
particular medications. While 12. Nitsche CJ, Jamieson N,
searching for another more Lerch MM. Drug
common cause, the temporal induced pancreatitis.
Best Pract Res Clin
association of medication use with Gastroenterol.
development of the episode 2010;24:143-55.
[PMID: 20227028]
should be evaluated. The clinician doi:10.1016/j.
bpg.2010.02.002
must recognize that drug-induced 13. Cheng CL, Sherman S,
pancreatitis can occur at any point Watkins JL. Risk factors
for post-ERCP pancreati-
in the course of a medication regi- tis: a prospective multi-
men, from a hypersensitivity reac- center study. Am J
Gastroenterol. 2006;
tion at or shortly after initiation to 101:139-47. [PMID:
an idiosyncratic reaction after 16405547]
Comments
Most common cause
Alcohol-related disease usually occurs only after >10–15 y of excessive drinking
More common in older patients, HIV-positive persons, and those receiving
immunomodulating agents or glucagon-like peptide-1 agonists
2%–20% of cases, particularly if performed in young females with suspected
sphincter of Oddi dysfunction
Usually with extremely elevated triglyceride levels (>1000 mg/dL)
Commonly caused by hyperparathyroidism or cancer; can be a trigger by
increasing activation of trypsinogen
Hereditary; research has linked gene mutations in cationic trypsinogen (PRSS1),
SPINK1, CTCR, CASR, or CFTR genes with acute and chronic pancreatitis
Usually occurs in younger patients and is often associated with inflammatory
bowel disease
Includes viruses (mumps, coxsackievirus, cytomegalovirus, varicella, herpes sim-
plex virus, HIV), bacteria (Mycoplasma, Legionella, Leptospira, Salmonella),
parasites (Toxoplasma, Cryptosporidium, Ascaris), and fungi (Aspergillus)
More likely if cysts involve or obstruct the main duct, such as pancreatic intra-
ductal papillary mucinous tumor
Accounts for approximately 5%–10% of cases; often subsequently found to be
due to an underlying genetic cause
Controversial, so all other causes should be excluded first
Focal pancreatitis can indicate an underlying mass
Rare; thickening of the duodenal wall is a clue
Such as ischemia related to bypass surgery
History is usually compelling
Endemic in parts of Asia and Africa
Rare even in patients with vasculitis
Extremely rare cause
In the Clinic ITC19 © 2021 American College of Physicians
 prolonged use; however, in many infections caused by parasites,
cases, the attack occurs soon after such as ascariasis, toxoplasmosis,
use of the drug is started. In general, and cryptosporidiosis; and viruses
14. Elmunzer BJ, Scheiman drug-induced acute pancreatitis is (cytomegalovirus, Epstein–Barr vi-
JM, Lehman GA, et al;
U.S. Cooperative for less common than was previously rus). Autoimmune processes lead-
Outcomes Research in
believed, and without strong evi- ing to pancreatitis, such as vasculitis
Endoscopy (USCORE). A
randomized trial of rectal dence for drug-related pancreatitis, and type 2 autoimmune pancreati-
indomethacin to prevent
post-ERCP pan-creatitis. use of essential medications can tis, are well described.
N Engl J Med. 2012;366:
1414-22. [PMID:
usually be continued (12). How can risk for a repeated
22494121] doi:10.1056
/NEJMoa1111103 An important iatrogenic risk factor episode be minimized?
15. Nordback I, Pelli H,
Lappalainen-Lehto R. The for acute pancreatitis is ERCP. The After a clear cause has been iden-
recurrence of acute alco- risk related to ERCP ranges from tified, efforts should be made not
hol-associated pan-creati-
tis can be reduced: a 2% to 20% depending on physi- only to eliminate the cause but
randomized controlled
trial. Gastroenterology.
cian-related factors, such as the also to provide counseling and
2009;136:848-55. [PMID: level of experience of the endo- education for the patient about
19162029] doi:10.1053
/j.gastro.2008.11.044 scopist performing the proce- avoidance of known risk factors.
16. Trivedi CD. Drug-induced
pancreatitis: an update.
dure; procedural indication When alcohol consumption has
J Clin Gastro-enterol. (especially sphincter of Oddi dys- been identified as the cause,
2005;39:709-16. [PMID:
16082282] function); female sex; and previ- patients should be evaluated for
17. Bellin MD, Kerdsirichairat
T, Beilman GJ. Total pan-
ous ERCP-related pancreatitis alcohol misuse or dependence.
createctomy with islet (13). Incidence is decreased by The patient should receive inten-
autotransplantation
improves quality of life in use of periprocedural rectal indo-
patients with refractory
sive counseling about the need to
methacin and possibly by prophy-
recurrent acute pancreati- abstain from alcohol to avoid
tis. Clin Gastroenterol lactic pancreatic duct stenting.
Hepatol. 2016;14:1317- repeated episodes of acute pan-
23. [PMID: 26965843]
doi:10.1016/j.cgh In a randomized controlled trial, creatitis or chronic pancreatitis, as
.2016.02.027 602 patients at elevated risk for well as the other well-known com-
18. Yadav D, Agarwal N. A crit-
ical evaluation of labora- post-ERCP pancreatitis were ran- plications of alcohol misuse and
tory tests in acute
pancreatitis. Am J Gastro- domly assigned to receive a single dependence. In this situation, one
enterol. 2002;97:1309- dose of rectal indomethacin or brief counseling session will not
18. [PMID: 12094843]
19. Liu KJ, Atten MJ, Lichtor placebo immediately after ERCP. suffice (15). In addition, referral
T. Serum amylase and
Pancreatitis developed in 27 of to alcohol specialty treatment
lipase elevation is associ-
ated with intracranial 295 patients (9.2%) in the indo- should improve abstinence,
events. Am Surg.
2001;67:215-9. [PMID: methacin group and 52 of 307 ideally with support to ensure
11270877]
(16.9%) in the placebo group that the patient receives this
20. Seno T, Harada H, Ochi K.
Serum levels of six pan- (P = 0.005). Moderate to severe care. Tobacco cessation should
creatic enzymes as related
pancreatitis developed in 13 also be recommended as a
to the degree of renal dys-
function. Am J Gastro- patients (4.4%) in the indometha- means of mitigating risk for
enterol. 1995;90:2002-5.
[PMID: 7485010] cin group and 27 (8.8%) in the pla- severe acute pancreatitis.
21. Manjuck J, Zein J, Carpati
C. Clinical significance of cebo group (P = 0.03). The trial
increased lipase levels on concluded that rectal indometha- As noted, several drugs have a
admission to the ICU.
cin significantly reduced incidence definite link to acute pancreatitis
Chest. 2005;127:246-50.
[PMID: 15653991] of the condition (14). (12). Physicians should be alert for
22. Wachter RM, Goldman L,
Hollander H. Hospital drug-induced pancreatitis in cer-
Medicine. Wolters Kluwer Careful patient selection and tain groups, such as patients with
Health; 2005.
23. Sch€utte K. Markers for
avoidance of ERCP unless it is underlying autoimmune condi-
predicting severity and clearly indicated will also tions on immunomodulators or
progression of acute pan-
creatitis. Best Pract Res decrease risk for acute pancreati- patients with HIV infection or can-
Clin Gastroenterol.
2008;22:75-90. [PMID:
tis resulting from this procedure. cer, who often take multiple medi-
18206814] doi:10.1016
/j.bpg.2007.10.013 Other less common causes are cations (16). However, even when
24. Gardner TB, Vege SS,
listed in Table 1. Rare causes of the association seems clear, ques-
Pearson RK. Fluid resusci-
tation in acute pancreati- unexplained acute pancreatitis tions may linger about whether
tis. Clin Gastroenterol
Hepatol. 2008;6:1070-6. include obstructive causes, such the drug or the underlying condi-
[PMID: 18619920] as cancer or mucinous cystic neo- tion for which it was prescribed
doi:10.1016/j.
cgh.2008.05.005 plasm; remote history of trauma; caused the pancreatitis.

© 2021 American College of Physicians ITC20 In the Clinic Annals of Internal Medicine February 2021
Patients who develop acute pan- In highly selected patients with
creatitis due to hypertriglyceride- refractory episodes of recurrent
mia should be counseled about acute pancreatitis for which no 25. Wu BU, Johannes RS,
lifestyle modifications, such as underlying cause can be pre- Sun X. Early changes in
blood urea nitrogen pre-
reducing intake of sugars and vented (hereditary or idiopathic dict mortality in acute
unhealthy fats, and should have pancreatitis), total pancreatec- pancreatitis. Gastro-
enterology. 2009;
aggressive medical interventions tomy with islet autotransplantation 137:129-35. [PMID:
to reduce triglyceride levels as has been shown to improve qual- 19344722]
doi:10.1053/j.
much as possible. ity of life (17). gastro.2009.03.056
26. Nichols MT, Russ PD.
Pancreatic imaging: cur-
rent and emerging tech-
nologies. Pancreas.
Prevention... Gallstones and excessive alcohol consumption are the most 2006;33:211-20.
common causes of acute pancreatitis. It is not possible to predict which [PMID: 17003640]
patients with these risk factors will develop the disease. Removal of gall- 27. Lankisch PG,
Struckmann K, Assmus
stones with cholecystectomy in patients with biliary colic, acute or chronic C. Do we need a com-
cholecystitis, and prior episodes of acute pancreatitis and removal of puted tomography ex-
amination in all patients
common bile duct stones with ERCP can help prevent recurrences. with acute pancreatitis
Alcohol and smoking cessation is critical to prevent further episodes of within 72 h after admis-
acute pancreatitis or development of chronic pancreatitis. Other less com- sion to hospital for the
detection of pancreatic
mon causes include hypertriglyceridemia and adverse effects of medica- necrosis. Scand J
tions, but alcohol and gallstones should first be ruled out as sole or Gastroenterol.
2001;36:432-6. [PMID:
concurrent causes. Recurrent pancreatitis related to hypercalcemia is best 11336171]
prevented through treatment of the underlying cause. Iatrogenic acute 28. Arvanitakis M, Delhaye
pancreatitis due to ERCP can be reduced by careful patient selection and M, De Maertelaere V.
Computed tomography
use of rectal indomethacin. Obstructive causes due to cysts or cancer and magnetic resonance
should generally be treated surgically. imaging in the assess-
ment of acute pancreati-
tis. Gastroenterology.
2004;126:715-23.
CLINICAL BOTTOM LINE [PMID: 14988825]
29. Makary MA, Duncan
MD, Harmon JW. The
role of magnetic reso-
nance cholangiography
in the management of
patients with gallstone
Diagnosis pancreatitis. Ann Surg.
2005;241:119-24.
What history and examination A detailed history of the type, quan- [PMID: 15621999]
30. Liu CL, Lo CM, Chan JK.
findings are helpful in tity, and frequency of alcohol and Detection of choledocho-
lithiasis by EUS in acute
diagnosing acute pancreatitis? tobacco use is critical. Careful his- pancreatitis: a prospec-
The most common presenting tory should assess for hyperlipid- tive evaluation in 100
consecutive patients.
symptom is abdominal pain, clas- emia; abdominal trauma; similar Gastrointest Endosc.
previous episodes; prior ERCP; or 2001;54:325-30.
sically described as occurring in [PMID: 11522972]
the epigastrium and radiating to worrisome signs of cancer, includ- 31. Lai R, Freeman ML, Cass
OW. Accurate diagnosis
the back. The pain is typically ing weight loss and anorexia. A of pancreas divisum by

severe and persistent without alle-
viating or relieving factors and is
often associated with nausea and
vomiting. Occasionally, patients
will feel worsening of pain in a
supine position that is relieved by
sitting.
In patients with suspected acute
pancreatitis, a detailed history
should address the potential
causes listed in Table 1. Previous
cholecystectomy for gallstones in
a person with no or minimal alcohol
use increases the likelihood of pan-
creatitis due to retained common
bile duct stones or microlithiasis.
detailed medication list must be linear-array endoscopic
ultrasonography.
reviewed, focusing on the likeli- Endoscopy. 2004;36:
705-9. [PMID:
hood of a drug being the cause as 15280976]
well as the timing of use (11). 32. Sedlack R, Affi A,
Vazquez-Sequeiros E.
Utility of EUS in the eval-
On physical examination, vital uation of cystic pancre-
atic lesions. Gastrointest
signs, including pulse, blood pres- Endosc. 2002;56:543-7.
[PMID: 12297771]
sure, and respiratory rate, must be 33. Gardner TB, Olenec CA,
assessed to evaluate hydration Chertoff JD. Hemocon-
centration and pancre-
status and indicate the severity of atic necrosis: further
pancreatitis. Tachycardia and hy- defining the relation-
ship. Pancreas.
potension represent intravascular 2006;33:169-73.
depletion secondary to fluid [PMID: 16868483]
34. Johnson CD. Persistent
sequestration seen in more severe organ failure during the
first week as a marker of
cases. Patients are often febrile fatal outcome in acute
due to the development of sys- pancreatitis. Gut.
2004;53:1340-4.
temic inflammatory response [PMID: 15306596]

February 2021 Annals of Internal Medicine In the Clinic ITC21 © 2021 American College of Physicians

35. Brown A, Orav J. Hemo-
concentration is an early
marker for organ failure and
necrotizing pancreatitis.
Pancreas. 2000;20:367-72.
[PMID: 10824690]
36. Blum T, Maisonneuve P,
Lowenfels AB. Fatal outcome in
acute pancreatitis: its occurrence
and early prediction. Pancrea-
tology. 2001;1:
237-41. [PMID: 12120201]
37. De Bernardinis M, Violi V,
Roncoroni L, et al.
Discriminant power and
information content of
Ranson's prognostic signs
in acute pancreatitis: a
meta-analytic study. Crit
Care Med. 1999;27:2272-
83. [PMID: 10548220]
38. Banks PA, Freeman ML;
Practice Parameters
Committee of the American
College of Gastroenterology.
Practice guidelines in acute
pancreatitis. Am J
Gastroenterol.
2006;101:2379-400.
[PMID: 17032204]
39. Johnson CD, Toh SK.
Combination of APACHE-II
score and an obesity score
(APACHE-O) for the predic-
tion of severe acute pan-
creatitis. Pancreatology.
2004;4:1-6. [PMID:
14988652]
40. Chatzicostas C,
Roussomoustakaki M,
Vlachonikolis IG.
Comparison of Ranson,
APACHE II and APACHE III
scoring systems in acute
pancreatitis. Pancreas.
2002;25:331-5. [PMID:
12409825]
41. Blamey SL, Imrie CW,
O’Neill J. Prognostic fac-
tors in acute pancreatitis.
Gut. 1984;25:1340-6.
[PMID: 6510766]
42. Wu BU, Johannes RS, Sun
X. The early prediction of
mortality in acute pancre-
atitis: a large population-
based study. Gut.
2008;57:1698-703.
[PMID: 18519429]
doi:10.1136/gut
.2008.152702
43. Papachristou GI, Muddana
V, Yadav D. Comparison of
BISAP, Ranson's, APACHE-II,
and CTSI scores in predict-
ing organ failure, complica-
tions, and mortality in acute
pancreatitis. Am J
Gastroenterol.
2010;105:435-41. [PMID:
19861954] doi:10.1038/
ajg.2009.622
44. Mortele KJ, Wiesner W,
Intriere L. A modified CT
severity index for evaluat-
ing acute pancreatitis:
improved correlation with
patient outcome. AJR Am
J Roentgenol. 2004;
183:1261-5. [PMID:
15505289]
45. Lobo SM, Lobo FR, Bota
DP. C-reactive protein lev-
els correlate with mortality
and organ failure in crit-
ically ill patients. Chest.
2003;123:2043-9. [PMID:
12796187]
© 2021 American College of Physicians
syndrome (SIRS). Jaundice usually
indicates biliary obstruction. The
clinician should perform a careful
abdominal examination, focusing
especially on auscultation for bowel
sounds, location of pain, guarding
(usually severe), rebound, and dis-
tention. Peritoneal signs are often
not found given that the pancreas
is located in the retroperitoneum.
Distention with absent bowel
sounds often indicates ileus.
Ecchymosis in the flanks (Grey
Turner sign) or around the umbili-
cus (Cullen sign) is indicative of
blood in the abdomen from pan-
creatic necrosis; both are rarely
encountered. Mental status
impairment is also an indicator of
more severe pancreatitis and may
result from septicemia, hypoxe-
mia, electrolyte imbalance, or
alcohol use. As such, simple bed-
side assessments of mental
capacity, such as the Glasgow
Coma Scale, should be consid-
ered. Multiorgan dysfunction sig-
nifies a more severe episode with
impending complications, such as
pancreatic necrosis.
Presence of gallstones and a his-
tory of fever, focal right upper
quadrant pain, and jaundice
(Charcot biliary triad) suggest
ascending cholangitis, but these
symptoms may be due only to the
inflammatory process associated
with acute pancreatitis.
What laboratory tests are used
to evaluate acute pancreatitis?
Elevation of serum amylase and/
or lipase levels to at least 3 times
the upper limit of normal is a key
component of diagnosing acute
pancreatitis. Measurement of se-
rum amylase levels has excellent
sensitivity but low specificity, sig-
nifying a high false-positive rate
(18). Other causes of elevated se-
rum amylase levels include disor-
ders of the salivary glands and
fallopian tubes, intestinal ische-
mia, perforated peptic ulcer, and
chronic renal insufficiency. To
improve specificity, the level of
ITC22 In the Clinic
the serum amylase or lipase needs
to be 3 times normal. Measure-
ment of lipase levels is more sensi-
tive and specific than that of amy-
lase levels in acute alcoholic
pancreatitis or when patients pres-
ent to the emergency department
days after disease onset because
these levels remain elevated for
longer. However, lipase can also
be falsely elevated in cases of renal
insufficiency and head trauma or
an intracranial mass as well as in
patients receiving heparin therapy
(through activation of lipoprotein
lipase) (19, 20). Elevated serum
lipase levels are also common
among critically ill patients in the
intensive care unit (ICU) (21).
Simultaneous measurement of am-
ylase and lipase levels does not
seem to improve diagnostic accu-
racy (18). There is no need to fol-
low patients with serial measure-
ments because these levels are not
predictors of severity and basing
clinical decision making on them
can lead to mismanagement. It is
critical for the clinician to be mind-
ful of the normal upper limits of
the respective amylase/lipase lev-
els because these vary significantly
among medical laboratories.
No enzyme assay can assess the
severity or cause of an episode of
acute pancreatitis. Therefore, the
degree of elevation of amylase
and/or lipase cannot predict dis-
ease severity. Serum C-reactive
protein at 48 hours is the best
available laboratory marker of
severity.
Liver enzymes should also be
routinely checked to diagnose
gallstone pancreatitis. Elevated
alanine aminotransferase level
(>150 IU/L) has a 95% positive
predictive value and a specificity
of 96% but sensitivity of less than
50% for gallstones as a cause of
acute pancreatitis; the accuracy
of aspartate aminotransferase is
similar (22). Liver tests can also be
used to evaluate for direct hyper-
Annals of Internal Medicine February 2021
bilirubinemia associated with
ascending cholangitis.
Triglyceride levels should be
evaluated because levels above
1000 mg/dL can precipitate
acute pancreatitis that is often
severe. Elevated values less than
1000 mg/dL are often seen in
acute pancreatitis as a secondary
lipemia from pancreatic inflam-
mation and should not be con-
fused with hypertriglyceridemia
as a primary cause.
The presence of leukocytosis on
a complete blood count usually
results from acute pancreatic
inflammation alone and is not a
sign of an underlying infectious
process. Increased hematocrit
and blood urea nitrogen levels
may reveal hemoconcentration,
which indicates fluid sequestra-
tion and is a worrisome predictor
of severity (23, 24). Early changes
in serial blood urea nitrogen lev-
els provide the most useful assess-
ment of response to initial fluid
resuscitation (25).
An acute decrease in hemoglobin
level in an unstable patient may
represent hemorrhagic pancreati-
tis. Patients with pancreatitis may
also develop disseminated intra-
vascular coagulopathy, perhaps
due to circulating pancreatic
enzymes or to vascular injury pre-
cipitating consumption of coagu-
lation factors.
What other diagnoses should
clinicians consider?
The clinical presentation of upper
abdominal pain with nausea, vomit-
ing, and fever has a broad differen-
tial diagnosis (Table 2). Although
peptic ulcer perforation often
mimics this presentation, it is distin-
guished by free air seen on imag-
ing studies. Acute cholecystitis,
symptomatic choledocholithiasis,
and ascending cholangitis are typi-
cally described as causing right
upper quadrant pain but can also
present with epigastric pain similar
to that of acute pancreatitis. Normal
February 2021 Annals of Internal Medicine
serum amylase and lipase levels as
well as characteristic imaging find-
ings, such as gallbladder wall thick-
ening (cholecystitis) or common
bile duct stones (choledocholithia-
sis), help differentiate biliary dis-
ease from acute pancreatitis but, as
noted, acute pancreatitis may also
present with gallstone-related bili-
ary obstruction, and it can be diffi-
cult to determine the primary
cause. Patients with intestinal
obstruction will have abdominal
distention, colicky abdominal pain,
and an obstructive bowel pattern
on imaging. They may also have
elevated serum amylase levels, but
these usually do not reach 3 times
the upper limit of normal. Mesent-
eric ischemia should be suspected
in patients with underlying vascular
or cardiac disease. Pain associated
with mesenteric ischemia is usually
postprandial and is often subjec-
tively worse than findings on physi-
cal examination (“pain out of
proportion to exam”), and on rare
occasions, an abdominal bruit may
be heard. Table 2 lists additional
causes of upper abdominal pain
that should be considered in the
differential diagnosis of acute
pancreatitis.
What is the role of imaging
studies in the evaluation of
acute pancreatitis?
Imaging plays an important role in
identifying the cause of the attack
and assessing severity (26). How-
ever, in general, imaging is not
used to determine the presence
of acute pancreatitis unless the di-
agnosis is in doubt. A plain ab-
dominal radiograph may show
nonspecific signs of acute pancre-
atitis, such as a sentinel loop
(localized ileus involving the jeju-
num), colon cutoff sign (isolated
distention of the transverse colon),
duodenal distention with air and
fluid, pleural effusion localized to
the left thorax, or radio-opaque
gallstones. In cases of abdominal
distention with acute pain, the
radiograph may reveal free air
In the Clinic ITC23
46. Sinha A, Cader R,
Akshintala VS. Systemic
inflammatory response
syndrome between 24
and 48 h after ERCP pre-
dicts prolonged length of
stay in patients with post-
ERCP pancreatitis: a retro-
spective study.
Pancreatology.
2015;15:105-10. [PMID:
25728146] doi:10.1016/j.
pan.2015.02.005
47. Lankisch PG, Weber-Dany
B, Hebel K. The harmless
acute pancreatitis score: a
clinical algorithm for rapid
initial stratification of non-
severe disease. Clin
Gastroenterol Hepatol.
2009;7:702-5. [PMID:
19245846] doi:10.1016/j.
cgh.2009.02.020
48. Crockett SD, Wani S, Gardner
TB, et al; American
Gastroenterological Association
Institute Clinical Guidelines
Committee. American
Gastroenterological Association
Institute guideline on initial
management of acute pancre-
atitis. Gastroenterology.
2018;154:1096-101. [PMID:
29409760] doi:10.1053/j.
gastro.2018.01.032
49. Wu BU, Hwang JQ,
Gardner TH. Lactated
Ringer's solution
reduces systemic inflam-
mation compared with
saline in patients with
acute pancreatitis. Clin
Gastroenterol Hepatol.
2011;9:710-717.e1.
[PMID: 21645639]
doi:10.1016/j.
cgh.2011.04.026
50. Bakker OJ, van Brunschot
S, van Santvoort HC, et al;
Dutch Pancreatitis Study
Group. Early versus on-
demand nasoenteric tube
feeding in acute pancreati-
tis. N Engl J Med.
2014;371:1983-93. [PMID:
25409371] doi:10.1056/
NEJMoa1404393
51. Villatoro E, Mulla M.
Antibiotic therapy for prophy-
laxis against infection of pan-
creatic necrosis in acute
pancreatitis. Cochrane
Database Syst Rev. 2010:
CD002941. [PMID:
20464721] doi:10.1002/
14651858.CD002941.pub3
52. van Santvoort HC, Besselink
MG, Bakker OJ, et al; Dutch
Pancreatitis Study Group. A
step-up approach or open
necrosectomy for necrotizing
pancreatitis. N Engl J Med.
2010;362:1491-502. [PMID:
20410514] doi:10.1056/
NEJMoa0908821
53. Gardner TB, Coelho-
Prabhu N, Gordon SR.
Direct endoscopic
necrosectomy for the
treatment of walled-off
pancreatic necrosis:
results from a multicen-
ter U.S. series.
Gastrointest Endosc.
2011;73:718-26.
[PMID: 21237454]
doi:10.1016/j.
gie.2010.10.053
© 2021 American College of Physicians
 Table 2. Differential Diagnosis of Acute Pancreatitis
Disease
Perforated viscus, especially peptic ulcer
Acute cholecystitis and biliary colic
Ascending cholangitis
Intestinal obstruction
Mesenteric vascular occlusion
Dissecting aortic aneurysm
Renal colic
Myocardial infarction
Connective tissue disorders with vasculitis
Appendicitis
Ectopic pregnancy
Pneumonia
54. Yuan X, Xu B, Wong M.
The safety, feasibility, and
cost-effectiveness of early
laparoscopic cholecystec-
tomy for patients with
mild acute biliary pancrea-
titis: a meta-analysis.
Surgeon. 2020. [PMID:
32709425] doi:10.1016
/j.surge.2020.06.014
55. Petrov MS, van Santvoort
HC, Besselink MG. Early
endoscopic retrograde
cholangiopancreatography
versus conservative man-
agement in acute biliary
pancreatitis without chol-
angitis: a meta-analysis of
randomized trials. Ann
Surg. 2008;247:250-7.
[PMID: 18216529]
doi:10.1097/
SLA.0b013e31815edddd
© 2021 American College of Physicians
Characteristics
Sudden onset of pain that increases over
30–60 min
Epigastric or right upper quadrant pain
that radiates to right shoulder or
shoulder blade
Fever, right upper quadrant pain, and
jaundice (Charcot triad), plus altered
mental status and shock (Reynold
pentad)
Constant wave-like pain; patient lying still
Classic triad is postprandial abdominal
pain, weight loss, and abdominal bruit
Sudden onset; pain may radiate to the
lower extremities
Flank pain radiates to the genitals; dysuria
may be present
Movement alleviates pain
Upper abdominal or chest pain
Acute pancreatitis can be due to vasculitis
Pain may start in epigastrium or
periumbilical then migrate to right lower
quadrant
Sudden onset of pain; menstrual
abnormalities often precede pain
Fever, malaise, and other respiratory
symptoms (dyspnea, cough, sputum
production, chest pain) usually present
showing a perforated viscus as
the cause of pain. Radiographs
may also occasionally reveal
nephrolithiasis as a cause of renal
colic.
The initial imaging study of choice
is ultrasonography of the right
upper quadrant because it is read-
ily available, noninvasive, inexpen-
sive, and relatively sensitive
(>90%) for diagnosing gallstone
disease. The presence of gall-
stones and/or dilatation of the
common bile duct supports
stones as the cause of acute pan-
creatitis, but the distal common
bile duct and pancreas body and
tail (because they are located in
the retroperitoneum) are fre-
quently obscured by overlying
bowel gas and therefore limit the
ITC24 In the Clinic Annals of Internal Medicine
Findings
Intraperitoneal air present
Liver enzyme levels often elevated;
ultrasonography may show thickened
gallbladder, pericholecystic fluid
Abnormal liver function test results in an
obstructive pattern
Obstructive pattern can be seen on
computed tomography scan or
abdominal series
Discrepancy between symptoms (severe
pain) and examination (benign
abdominal findings)
Differential pulse pressure between
extremities
Urinalysis with active sediment
Stone seen on computed tomography
scan
Electrocardiography usually abnormal
Other signs of vasculitis usually present
(skin, joint, eye, and kidney
involvement)
Ultrasonography and computed tomog-
raphy aid in diagnosis
Rapid drop in hematocrit and
intraperitoneal pelvic fluid on imaging
should raise suspicion
Changes on physical examination of the
chest and abnormalities on chest
radiography possibly due to acute
respiratory distress syndrome or pleural
effusion
sensitivity of ultrasonography for
diagnosing gallstone-associated
pancreatitis.
In patients in whom the diagnosis
of acute pancreatitis is question-
able after a careful history, physi-
cal examination, and pancreatic
enzyme measurement, a contrast-
enhanced, thin-sliced, triple-
phase computed tomography
(CT) provides excellent pancreatic
imaging and can identify other
causes of abdominal pain. CT can
also be useful to assess the sever-
ity of pancreatitis and identify
complications, such as necrosis
(infected or not), pseudocyst for-
mation, and vascular and extrap-
ancreatic complications (27).
Figure 1 demonstrates the find-
ings of severe necrotizing
February 2021

Figure 1. Axial computed tomography image on admission of a patient with severe
acute pancreatitis.
Peripancreatic stranding (black arrow) indicates inflammatory changes, and diffuse
hypoperfusion of the parenchyma (white arrow) indicates pancreatic necrosis.
pancreatitis. However, a CT scan
may not show signs of pancreatitis
or its complications early in the
disease course and therefore is
not recommended at admission
unless there is a diagnostic ques-
tion. In addition, intravenous con-
trast may accelerate renal injury.
In patients with contrast allergy,
magnetic resonance imaging
(MRI) is a higher-cost alternative
for diagnosing and evaluating the
severity of acute pancreatitis. It is
also more sensitive in detecting
microlithiasis in the gallbladder
and common bile duct and pan-
creatic duct disruption (28). In
patients with renal impairment,
MRI without gadolinium can detect
necrosis and provide good imag-
ing of bile and pancreatic ducts
based on T2-weighted images.
Among other imaging modalities,
magnetic resonance cholangio-
pancreatography (MRCP) is nonin-
vasive; has high sensitivity (>90%)
for choledocholithiasis; and can
identify other anatomical abnor-
malities, such as pancreas divisum,
pancreatic duct abnormalities,
February 2021 Annals of Internal Medicine
annular pancreas, and mucinous
cystic neoplasms in the pancreas
(29). It also can exclude the pres-
ence of a retained stone or debris
if there is a high index of clinical
suspicion.
Secretin-enhanced MRCP is useful
for evaluating pancreatic function
and anatomy when underlying
chronic pancreatitis is suspected.
However, because secretin stimu-
lates pancreatic secretion, it gen-
erally should not be obtained
during an episode of acute
pancreatitis.
Endoscopic ultrasonography is
both sensitive and specific in iden-
tifying small (for example, ≤5 mm)
gallstones in the bile ducts (30),
underlying chronic pancreatitis,
small tumors obstructing the pan-
creatic duct, and other anatomical
abnormalities as causes of acute
pancreatitis. Although more inva-
sive than MRI, it can detect smaller
stones and can be used when MRI
is not possible (for example, in
critically ill patients or when it is
contraindicated, such as in
In the Clinic ITC25
patients with a cardiac pacer) (31,
32). It can also be used in combi-
nation with ERCP—a patient can
be evaluated for suspected chole-
docholithiasis with endoscopic
ultrasonography and then subse-
quently undergo ERCP during the
same endoscopic session if stones
are present.
What factors predict severity of
acute pancreatitis?
Patients should be stratified by
risk for severe morbidity and
death related to acute pancreatitis
because of the disease's protean
manifestations, its unpredictable
course, and the need to identify
persons who require intensive
care. The Atlanta Classification of
Acute Pancreatitis was developed
in 1992 and revised in 2012 to
standardize what was a heteroge-
neous set of criteria to diagnose
the disease and assess severity
(1). The revised Atlanta Classifi-
cation severity criteria are shown
in Table 3. This classification relies
heavily on the presence of local-
ized complications, such as pan-
creatic fluid collections, and the
presence or absence of organ fail-
ure and is considered the gold
standard for classifying the sever-
ity of acute pancreatitis.
To fully understand the rationale
behind the Atlanta Classification's
development, it is important to
consider the natural history of
acute pancreatitis. There is a peak
in mortality usually within the first
week of onset and another 2 to 6
weeks after onset. In the first week,
disease severity is usually reflected
by the extent of organ failure. After
that, mortality can be better pre-
dicted by the presence of local
complications, such as infection,
thromboses, and fluid collections.
Therefore, when a patient first
presents, clinicians should be alert
to the possibility of organ failure
(33, 34). As expected, progression
from single to multiorgan failure is
a predictor of increased mortality
© 2021 American College of Physicians
 collections develop from intersti-
Table 3. Revised Atlanta Classification for Severity of Acute Pancreatitis
tial pancreatitis, and acute ne-
Mild acute pancreatitis crotic collections arise from
Absence of any extrapancreatic organ failure, including failure in respiratory, necrotizing pancreatitis. After 4
cardiovascular, and renal systems weeks, acute fluid collections can
Absence of local complications* or systemic complications develop into pancreatic pseudo-
cysts, which have an encapsulated
Moderately severe acute pancreatitis wall but no solid debris.
Presence of complications, including: Pseudocysts are in fact rare
Peripancreatic fluid collection or peripancreatic necrosis because acute fluid collections
Systemic complications without persistent organ failure usually resolve. However, acute
necrotic collections form into
Severe acute pancreatitis walled-off necrosis, which does
Organ failure that persists after 48 h† contain solid debris (Figure 2).
* Such as pseudocyst or pancreatic necrosis.
Appropriate classification of pan-
† Defined as acute respiratory failure (PaO2–FIO2 ratio <400), shock (systolic blood creatic fluid collections is impor-
pressure ≤90 mm Hg), and/or renal failure (creatinine ≥1.4 mg/dL). tant because their treatment
varies significantly.

(35, 36). Coagulopathy bodes
poorly for patients, as indicated by
platelet count less than 100  109
cells/L, fibrinogen level less than
100 mg/dL, and fibrin split products
greater than 80 mg/mL. Similarly,
low serum calcium levels (≤7.5 mg/
dL) carry a poor prognosis.
The Atlanta criteria also identified
the development of local compli-
cations (acute pancreatic/peri-
pancreatic necrotic collections) as
indicative of severe acute
Figure 2. Representative axial computed tomography images of acute fluid collection
(A), acute necrotic collection (B), pancreatic pseudocyst (C), and walled-off pancre-
atic necrosis (D).
pancreatitis. Pancreatic necrosis is
demonstrated by poor perfusion
and nonenhancement on a CT
scan of more than 3 cm or more
than 30% of the pancreas (1).
Pancreatic fluid collections can be
divided into 4 types depending
on their cause and timing. Acute
pancreatic and/or peripancreatic
fluid collections and acute ne-
crotic collections develop within
4 weeks and do not have an
encapsulated wall. Acute fluid
Various other classifications have
been developed to assess the se-
verity of acute pancreatitis early in
the disease course, including the
Ranson criteria, the Acute
Physiology and Chronic Health
Evaluation (APACHE-II and III)
scale, the modified Glasgow
prognostic criteria (also known as
the Imrie scoring system), the
Bedside Index for Severity in
Acute Pancreatitis (BISAP) score,
and the modified CT severity
index (37–44). However, an unmet
need exists for a marker or system
that has a strong positive predic-
tive value for early identification of
a patient who develops moder-
ately severe or severe disease
(approximately 20% of all
patients).
It is important to note that serum
amylase and lipase levels cannot
predict the severity of acute pan-
creatitis. However, C-reactive pro-
tein has been widely used to
predict severity, and in critically ill
patients, values over 150 mg/dL
at 24 and 48 hours have been
shown to be associated with
increased risk for organ failure
and death (45). The presence of
persistent SIRS at 48 hours after
admission has also been shown to
predict severity (46).

© 2021 American College of Physicians ITC26 In the Clinic Annals of Internal Medicine February 2021
 Diagnosis... Diagnosis of acute pancreatitis is based on the presence of
at least 2 of 3 features: abdominal pain; increased pancreatic enzyme, am-
ylase, and/or lipase levels to 3 or more times the upper limit of normal;
and imaging tests showing characteristic findings. Ultrasonography of the
right upper quadrant may reveal stones or biliary duct dilatation, and CT
can assess for pancreatic necrosis or pancreatic fluid collection formation,
although it should be delayed until several days after admission. MRI and
MRCP offer alternatives in select situations but are more costly. Assessing
the severity of the attack involves using clinical laboratory parameters;
imaging; and standard measurements, such as the revised Atlanta
Classification, but current systems are not perfect.

CLINICAL BOTTOM LINE

What are the indications for
hospitalization and for
intensive care for a patient
with acute pancreatitis?
Patients with acute pancreatitis
should be hospitalized until they
have been observed for a suffi-
cient period to evaluate disease
severity and progression. Essential
management includes aggressive
intravenous fluid resuscitation
with no fluids or solids by mouth.
Patients often require pain man-
agement with intravenous medica-
tions; opiates are typically used and
must be monitored for adverse
effects, such as respiratory depres-
sion. Stable patients with a mild epi-
sode who have a history of multiple
episodes can occasionally be man-
aged on an outpatient basis (47).
Such tests as ERCP are usually
done in an inpatient setting when
indicated. Severe acute pancreati-
tis requires close inpatient moni-
toring, and the patient should be
transferred to the ICU if organ
failure develops (48). In elderly
patients with underlying cardio-
vascular disease, aggressive fluid
resuscitation should be adminis-
tered in an ICU and may require a
central venous catheter for more
accurate fluid monitoring. Transfer
to a specialized monitoring unit
(not necessarily an ICU) should be
considered for patients with high
body mass index (>30 kg/m2),
decreased urine output (<50 mL/
h), tachycardia (pulse rate >120
beats/min), oxygen saturation
(SaO2) less than 90%, signs of ence-
phalopathy, or a need for addi-
tional narcotics.
How should clinicians manage
fluids in a patient with acute
pancreatitis?
Fluid resuscitation is a critical
component of management of
patients with acute pancreatitis
because they can experience a
significant loss of intravascular vol-
ume due to third-spacing and
increased permeability from
release of inflammatory mediators
(24). Compromised intravascular
volume can lead to decreased
perfusion of the pancreas and
such complications as pancreatic
necrosis and renal failure. Fluid
administration should be guided
by vital signs; clinical examination
(neck veins, pulmonary conges-
tion); urine output; and change in
hematocrit at admission, 12 hours,
and 24 hours. Lactated Ringer's
solution seems to be superior to
normal saline, based on clinical
trial data supporting its use in
mitigating SIRS and decreasing
C-reactive protein levels (49). It is
Treatment
critical that early fluid resuscitation
occur as soon as possible after the
diagnosis is established.
How should clinicians manage
the nutritional needs of a
patient with acute pancreatitis?
In mild acute pancreatitis, nutri-
tional support is often not neces-
sary. Once pain has diminished
along with nausea and vomiting,
oral nutrition can be started. It can
begin with low-fat solids and clini-
cal monitoring for change in pain
and symptoms of nausea and
vomiting. Resolution of imaging
findings and normalization of amy-
lase and lipase levels are not help-
ful in prognosticating recovery, so
the diet should be advanced on
the basis of how the patient feels.
Patients with moderate or severe
pancreatitis at risk for necrosis
should be started on enteral nutri-
tion as soon as possible because
there is a clear mortality benefit in
those who receive early enteral
feeding. The primary benefit of
enteral over parenteral feeding is
a reduction in infectious complica-
tions, including bacterial translo-
cation from the intestine into the
inflamed pancreas leading to
infected pancreatic necrosis.
Patients can be started on a low-
fat oral diet within 72 hours after
admission if tolerated.

February 2021 Annals of Internal Medicine In the Clinic ITC27 © 2021 American College of Physicians
In a randomized trial of 208
patients with predicted severe
pancreatitis, patients were ran-
domly assigned to nasoenteric
tube feeding within 24 hours after
randomization (early group) or an
oral diet initiated 72 hours after
presentation (on-demand group),
with tube feeding provided if the
oral diet was not tolerated. There
were no significant differences
between the early group and the
on-demand group in the rate of
major infection (25% and 26%,
respectively; P = 0.87) or death
(11% and 7%, respectively; P =
0.33). This trial did not show supe-
riority of early nasoenteric tube
feeding compared with an oral
diet after 72 hours in reducing the
rate of infection or death in
patients with acute pancreatitis at
high risk for complications (50).
In addition, studies comparing
nasogastric with nasojejunal feed-
ing have not shown significant dif-
ferences in outcomes, but larger
comparative studies are required
before practice recommendations
are changed. However, parenteral
nutrition may be required in some
critically ill patients as well as
those with severe ileus if tube
feeds or oral feeding are not
tolerated.
potentially decreasing pancreatic
and biliary flow into the small
bowel lumen, but this has not
been confirmed in clinical studies.
Fentanyl, hydromorphone, and
morphine are the more commonly
used narcotics for pain control in
acute pancreatitis.
What is the role of antibiotics?
Antibiotics are not currently rec-
ommended for mild interstitial
pancreatitis or even for moderate
to severe pancreatitis with sterile
necrosis. Studies of prophylactic
administration of antibiotics to
decrease infectious complications
have been largely nonsupportive
of their use. A Cochrane review
found no benefit of antibiotics to
prevent infection of pancreatic ne-
crosis or mortality, with the possi-
ble exception of the b-lactam
imipenem, which was associated
with a significant decrease in pan-
creatic infection (51). The
reviewers concluded that better-
designed studies would be
required before antibiotic prophy-
laxis could be recommended.
However, antibiotics are required
to treat ascending cholangitis,
Figure 3. Intracavitary endoscopic debridement via the stomach for symptomatic
walled-off pancreatic necrosis.
infected pancreatic necrosis, or an
infected pancreatic fluid collec-
tion. When sepsis or infection is
suspected, a fever work-up should
be done with cultures and chest
radiography. If needed, CT-
guided needle aspiration of a ne-
crotic area of the pancreas should
be cultured for bacteria and fungi.
If the results of the work-up are
negative, antibiotic therapy
should be continued if the patient
has septicemia, organ failure, or at
least 30% necrosis of the pan-
creas. For an infected necrotic
pancreas, the choice of antibiotic
is guided by the culture. For
gram-negative organisms, options
include imipenem, meropenem,
ofloxacin, ciprofloxacin, or a third-
generation cephalosporin with
metronidazole. Patients with
infected pancreatic necrosis
should be closely observed to
assess for response, and most
recover with medical treatment
without the need for intervention.
Management of pancreatic fluid
collections has changed dramati-
cally in the past decade with rou-
tine use of minimally invasive
drainage and debridement

What other supportive care

may be beneficial?
Oxygen may reduce acute respi-
ratory distress syndrome that can
occur in the early stages of acute
pancreatitis. Pain management is
another key aspect of treatment.
Due to the severity of pain with
acute pancreatitis and the fre-
quent inability to tolerate oral
intake, parenteral narcotic analge-
sics are essential. Opiates are usu-
ally administered every 2 to 4
hours. A patient-controlled anal-
gesia pump offers an alternative
when boluses of pain medications
provide inadequate pain control.
Morphine has been theoretically
implicated in increasing pressure
in the sphincter of Oddi and

© 2021 American College of Physicians ITC28 In the Clinic Annals of Internal Medicine February 2021
techniques. Pancreatic fluid col-
lections should be intervened on
only if they are symptomatic (pain,
luminal obstruction, infection)
because most resolve spontane-
ously. The guiding principle for
acute fluid and necrotic collec-
tions is delaying intervention so
that an encapsulated wall can
mature; this generally will not
occur sooner than 3 to 4 weeks af-
ter onset of pancreatitis. Once an
encapsulated wall forms around
the acute collection, drainage pro-
cedures for pseudocysts and de-
bridement procedures for acute
necrotic collections can be per-
formed (Figure 3). Minimally inva-
sive endoscopic drainage and
debridement procedures are
favored over surgical techniques
because of their increased effi-
cacy, lower complication rate, and
lower cost (52, 53).
When should clinicians
consider consultation with a
gastroenterologist or surgeon?
For patients who have mild acute
pancreatitis with a known cause,
consultation is usually unneces-
sary. However, if the cause is
unclear or a patient has been
admitted with unexplained recur-
rent acute pancreatitis, a gastro-
enterology consultation may be
useful. In patients with more
severe attacks, gastroenterology
consultation can assist with man-
agement and monitoring for com-
plications, such as pancreatic fluid
collections. Also, when gallstone
pancreatitis due to choledocholi-
thiasis is suspected, consultation
for ERCP may be necessary.
Patients with mild interstitial pan-
creatitis due to gallstones should
have their gallbladder removed
before discharge because the
chance of a repeated attack after
discharge without surgery
approaches 50% (54).
What are the indications for
ERCP?
The presence of a retained bile
duct stone causing biliary obstruc-
tion seen on imaging is an indica-
tion for ERCP to perform biliary
sphincterotomy and stone re-
moval. Urgent ERCP is indicated if
cholangitis is suspected. In the ab-
sence of criteria for ascending
cholangitis, studies have found
that early ERCP is associated with
increased complications (55).
Patients presenting with compli-
cated acute pancreatitis due to a
disrupted pancreatic duct with a
pancreatic leak may also benefit
from ERCP and placement of a
pancreatic duct stent.

Treatment... Acute pancreatitis should be managed in the inpatient setting, with rare exceptions, and patients
with organ failure or severe comorbid conditions should be treated in the ICU. Intravenous fluid resuscitation with
lactated Ringer's solution is the most important initial approach to management, and failure of adequate resuscita-
tion is the most critical mistake made. Appropriate pain control and supportive care with oxygen supplementation
are other basic measures. In patients with moderate or severe pancreatitis, enteral nutrition is preferred to paren-
teral nutrition and should be started no sooner than 72 hours after admission if oral intake is not possible.
Antibiotics are recommended only for a documented infectious process and should not be used in severe acute
pancreatitis to prevent infected necrosis. ERCP should be performed only in the setting of concomitant ascending
cholangitis or worsening liver test results 24 hours after admission with a proven common bile duct stone.
Minimally invasive approaches should be used to treat mature, symptomatic pancreatic fluid collections. All
patients with biliary pancreatitis should be considered for cholecystectomy before discharge.

CLINICAL BOTTOM LINE

February 2021 Annals of Internal Medicine In the Clinic ITC29 © 2021 American College of Physicians
 Practice Improvement
What do professional
organizations recommend with
regard to the care of patients
with acute pancreatitis?
Two acute pancreatitis guidelines
have been published in the past
decade by the American College
of Gastroenterology (2013) and
the American Gastroenterological
Association (2018) (48, 56). Major
recommendations from these
guidelines are shown in Table 4.
What is the role of patient
education in the management
of acute pancreatitis?
Patient education plays an impor-
tant role in preventing recurrent
acute pancreatitis. Lifestyle meas-
ures, such as cessation of alcohol
consumption and smoking, are
critical. Education about the risks
of certain medications if impli-
cated in the initial episode should
also be provided with careful
monitoring. Dietary modification
and adherence to lipid-lowering
medications are both necessary in
patients with pancreatitis due to
hypertriglyceridemia. Patients
with acute pancreatitis should also
be warned about symptoms that
suggest recurrence of pancreatitis
or its complications.

Table 4. Selected Major Recommendations From Recent Acute Pancreatitis Guidelines

American College of Gastroenterology (2013) (56)

Contrast-enhanced computed tomography and/or magnetic resonance imaging of the pancreas should be reserved for patients
in whom the diagnosis is unclear or who fail to improve clinically within the first 48–72 h after hospital admission.
Transabdominal ultrasound should be performed in all patients with acute pancreatitis.
In patients older than 40 y, a pancreatic tumor should be considered as a possible cause of acute pancreatitis.
Genetic testing may be considered in young patients (aged <30 y) if no cause is evident and a family history of pancreatic
disease is present.
Patients with organ failure should be admitted to an intensive care unit or intermediary care setting whenever possible.
Aggressive hydration, defined as 250–500 mL of isotonic crystalloid solution per hour, should be provided to all patients, unless
cardiovascular and/or renal comorbidities exist.
Fluid requirements should be reassessed at frequent intervals within 6 h of admission and for the next 24–48 h.
Patients with acute pancreatitis and concurrent acute cholangitis should undergo ERCP within 24 h.
Routine use of prophylactic antibiotics in patients with severe acute pancreatitis is not recommended.

American Gastroenterological Association (2018) (48)

In patients with acute pancreatitis, the AGA suggests using goal-directed therapy for fluid management.
In patients with predicted severe acute pancreatitis and necrotizing acute pancreatitis, the AGA suggests against use of
prophylactic antibiotics.
In patients with acute biliary pancreatitis and no cholangitis, the AGA suggests against routine use of urgent ERCP.
In patients with acute pancreatitis, the AGA recommends early (within 24 h) oral feeding as tolerated, rather than keeping the
patient nil per os.
In patients with acute pancreatitis and inability to feed orally, the AGA recommends enteral rather than parenteral nutrition.
In patients with predicted severe or necrotizing pancreatitis requiring enteral tube feeding, the AGA suggests either the
nasogastric or the nasojejunal route.
In patients with acute biliary pancreatitis, the AGA recommends cholecystectomy during the initial admission rather than after
discharge.
In patients with acute alcoholic pancreatitis, the AGA recommends brief alcohol intervention during admission.

AGA = American Gastroenterological Association; ERCP = endoscopic retrograde cholangiopancreatography.

© 2021 American College of Physicians ITC30 In the Clinic Annals of Internal Medicine February 2021
 In the Clinic
Patient Information
In the Clinic https://medlineplus.gov/pancreatitis.html

Tool Kit
Information and handouts from the National Institutes of
Health's MedlinePlus.

Acute Pancreatitis
www.niddk.nih.gov/health-information/digestive
-diseases/pancreatitis
www.niddk.nih.gov/health-information/informacion
-de-la-salud/enfermedades-digestivas/pancreatitis
Information in English and Spanish from the National
Institute of Diabetes and Digestive and Kidney Diseases.

https://gastro.org/practice-guidance/gi-patient-center
/topic/pancreatitis
Information from the American Gastroenterological
Association.
Information for Health Professionals
www.gastrojournal.org/article/S0016-5085(18)30076-3
/fulltext
2018 guideline on initial management of acute pancreatitis
from the American Gastroenterological Association
Institute Clinical Guidelines Committee.

https://journals.lww.com/ajg/Fulltext/2013/09000
/American_College_of_Gastroenterology_Guideline_.6
.aspx
2013 guideline on management of acute pancreatitis from
the American College of Gastroenterology.

www.aafp.org/afp/2014/1101/p632.html
Information from the American Academy of Family
Physicians.

February 2021 Annals of Internal Medicine In the Clinic ITC31 © 2021 American College of Physicians

WHAT YOU SHOULD KNOW
ABOUT ACUTE PANCREATITIS
What Is Acute Pancreatitis?
The pancreas is a gland that is located behind the
stomach. It makes digestive fluid that helps to break
down food. Acute pancreatitis happens when
something blocks the flow of this fluid or attacks
the tissues of the pancreas, causing it to become
irritated and swollen. If not treated quickly,
acute pancreatitis can be deadly, so be sure to
be evaluated within 24 hours of when symptoms
start.
What Are the Symptoms?
• Severe, constant pain in the upper part of your
stomach that may spread to your back
• Stomach pain that gets worse after eating
• Nausea and vomiting
• Sweating
• Fever
What Causes It?
The most common causes of acute pancreatitis
are gallstones and alcohol use. Other causes,
such as elevated blood fat levels, medications,
and autoimmune diseases, are much less
common.
Am I at Risk?
Factors that put you at higher risk for acute pancre-
atitis include:
• Having gallstones
• Long-term, heavy alcohol use
• Taking certain medicines
• Having high levels of fat in your blood
• Having problems with the pancreas since birth
How Is It Diagnosed?
• Your doctor will perform a physical examination
and check your vital signs. He or she will review
any medicines you take and ask about factors
that may put you at risk for pancreatitis. This will
include asking about your alcohol or tobacco
use.
• Blood tests will be used to check for signs of
pancreatitis.
MedlinePlus
https://medlineplus.gov/pancreatitis.html
National Pancreas Foundation
https://pancreasfoundation.org/patient-information/acute-
pancreatitis
© 2021 American College of Physicians ITC32 In the Clinic
In the Clinic
Annals of Internal Medicine
• Imaging tests, such as an x-ray or ultrasound,
may be used to look at your pancreas and check
for causes of pancreatitis (like gallstones).
• More advanced imaging tests and interventions
may be necessary if you are very sick or do not
improve in the hospital.
How Is It Treated?
• Most patients with acute pancreatitis need to
be hospitalized. Most people feel better within a
week and can leave the hospital. Recovery may
take longer in more serious cases.
• While in the hospital, you may need to stop eat-
ing for a few days while your pancreas gets
better.
• Your doctor may give you medicines to help with
your pain. Fluids will be given through your veins
to keep you hydrated.
• You may need treatment for what is causing the
problem, such as surgery to remove a gallstone
Patient Information
or your gallbladder.
• After an episode of acute pancreatitis, it is impor-
tant to avoid anything that can cause another epi-
sode, such as alcohol, tobacco, certain medi-
cines, and fatty foods.
Questions for My Doctor
• What caused my pancreatitis?
• What kind of tests do I need?
• Could this happen again? How can I prevent it
from happening again?
• What food and drinks should I stay away from?
• Should I see other doctors?
For More Information
Annals of Internal Medicine February 2021