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CLINICAL GUIDELINE

419

American College of Gastroenterology Guidelines:

Management of Acute Pancreatitis

Scott Tenner, MD, MPH, JD, FACG¹, Santhi Swaroop Vege, MD, MACG², Sunil G. Sheth, MD³, Bryan Sauer, MD, MSci, FACG⁴,

Allison Yang, MD, MPH⁵, Darwin L. Conwell, MD, MSc, FACG⁶, Rena H. Yadlapati, MD, MHS, FACG⁷ and Timothy B. Gardner, MD, FACG⁸

Acute pancreatitis (AP), defined as acute inflammation of the pancreas, is one of the most common diseases of the

gastrointestinal tract leading to hospital admission in the United States. It is important for clinicians to appreciate that AP is

heterogenous, progressing differently among patients and is often unpredictable. While most patients experience symptoms

lasting a few days, almost one-fifth of patients will go on to experience complications, including pancreatic necrosis and/or

organ failure, at times requiring prolonged hospitalization, intensive care, and radiologic, surgical, and/or endoscopic

intervention. Early management is essential to identify and treat patients with AP to prevent complications. Patients with

biliary pancreatitis typically will require surgery to prevent recurrent disease and may need early endoscopic retrograde

cholangiopancreatography if the disease is complicated by cholangitis. Nutrition plays an important role in treating patients

with AP. The safety of early refeeding and importance in preventing complications from AP are addressed. This guideline will

provide an evidence-based practical approach to the management of patients with AP.

Am J Gastroenterol 2024;119:419-437. https://doi.org/10.14309/ajg.0000000000002645

INTRODUCTION

performed for preparation of this document. Similar to prior ACG

Acute pancreatitis (AP) is one of the most common diseases of the

guidelines, this guideline is structured in sections, each with rec-

gastrointestinal tract and leads to a tremendous emotional, physical,

ommendations or key concepts and summaries of the evidence

and financial burden for the patient. In the United States, there are

based on the PICO question. PICO is an acronym that includes the

almost 300,000 admissions annually for AP, resulting in more than 1

following: P 5 population/problem, I 5 intervention, C 5 com-

million patient days in the hospital at a cost over 2.5 billion dollars

parison, and O 5 outcome. PICO questions were developed by the

(1). The incidence of AP has been increasing by 2%-5% per year and

consensus of the authors and served as the basis for each recom-

varies between 3.4 and 73.4 cases per 100,000 worldwide (1,2). Al-

mendation and key concepts (Table 1). PICO questions were pri-

though the case fatality rate has decreased over time, the overall

marily used for the management of AP. For the diagnosis, etiology,

population mortality rate has remained unchanged with 5,000-9,000

and severity of AP, the PICO format was not used. Recommenda-

deaths reported annually (1). Advancements in the management of

tions were made based on the assessment of the quality of evidence

AP over the past decade have been associated with a decrease in

by the Grading of Recommendations Assessment, Development

mortality (3). In this context, a group of experts within the American

and Evaluation (GRADE) process (4) (Table 2).

College of Gastroenterology (ACG) were tasked to complete a sys-

The GRADE system result used to evaluate the quality of the

tematic review of the literature concerning AP and develop guide-

supporting evidence for each recommendation is listed in Table 2,

lines for the membership. In these guidelines, we first discuss the

following each recommendation. A strong recommendation is

diagnosis, etiology, and severity of AP. We then focus on the early

made when the benefits clearly outweigh the negatives and/or the

medical management of AP followed by a discussion of the man-

result of no action. Conditional is used when uncertainty remains

agement of complicated disease, most notably pancreatic necrosis.

about the balance of benefits and potential harms. Statements

The evolving issues of antibiotics, nutrition, endoscopic, radiologic,

with a strong recommendation are stated with we recommend,

and surgical interventions are also addressed.

whereas conditional recommendations are stated with we sug-

gest. The quality of evidence is classified from high to very low.

METHODOLOGY

High-quality evidence indicates that further research is not likely

A health science librarian was contracted to assist in the completion

to change the authors’ confidence in the estimate of the effect.

of a MEDLINE search through the OVID interface using the MeSH

Moderate-quality evidence is associated with moderate confi-

term acute pancreatitis limited to all clinical trials and meta-analysis

dence in the effect estimate, although further research would be

for years 1966-2022 limited to the English language literature. A

likely to have an impact on the confidence of the estimate.

review of clinical trials and reviews known to the authors was also

Low-quality evidence indicates that further study would have an

¹State University of New York, Health Sciences Center, Brooklyn, New York, USA;²Mayo Clinic, Rochester, Minnesota, USA;³Beth Israel Deaconess Medical

Center, Boston, Massachusetts, USA;⁴University of Virginia, Charlottesville, Virginia, USA;⁵Weill Cornell Medicine, New York, New York, USA;⁶University of

Kentucky, Lexington, Kentucky, USA;⁷University of California, San Diego, San Diego, California, USA;⁸Dartmouth-Hitchcock Medical Center, Lebanon, New

Hampshire, USA. Correspondence: Santhi Swaroop Vege, MD, MACG. E-mail: vege.santhi@mayo.edu.

Received June 8, 2023; accepted December 8, 2023; published online November 7, 2023

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Table 1. PICO questions that served as the basis for recommendations and key concepts

At admission

1. In patients with AP complicated by the SIRS and/or organ dysfunction, does admission to a monitored/ICU bed decrease mortality, the development of severe

disease, and/or decrease the LOS?

2. In patients with AP, will making patients NPO compared with allowing patients to eat and drink as tolerated result in a decreased risk of complications, prevent

recurrent disease, or decrease the length of stay?

3. In patients with mild AP who begin to receive oral feeding, does a liquid diet compared with a regular diet prevent complications, recurrent disease, or decrease

the length of stay?

4. In patients with AP, does early aggressive intravenous hydration compared with standard hydration result in a decreased risk of developing severe disease,

pancreatic necrosis, and mortality?

5. In patients with AP, does early frequent monitoring of BUN and/or HCT decrease the risk of developing severe disease, necrosis, LOS, and/or mortality?

6. In patients with AP, is there a benefit to early routine imaging (US and/or CT) compared with case specific, as needed imaging?

After admission

7. In patients with acute biliary pancreatitis, does early ERCP (before 24 and 72 hr) compared with maximal medical therapy decrease morbidity and mortality?

8. In patients with AP who do not improve after the first 72 hr, does early cross-sectional imaging to identify the presence of necrosis or other anatomic

complications compared with a conservative approach decrease morbidity or mortality?

AP complicated by necrosis

9. In patients with AP complicated by pancreatic necrosis, does enteral (nasogastric or nasojejunal) feeding compared with early oral feeding result in a difference

in infectious complications, LOS, and mortality?

10. In patients with AP complicated by pancreatic necrosis, do prophylactic antibiotics compared with as-need antibiotic therapy decrease the incidence of

infectious complications, infected pancreatic necrosis, LOS, and mortality?

11. In patients with suspected infected pancreatic necrosis, does a CT fine-needle aspiration compared with immediate antibiotic therapy result in better

outcomes, decreased infectious complications, sepsis, LOS, and mortality?

Preventing AP and recurrence

12. In patients with idiopathic pancreatitis, will additional imaging (e.g., EUS, MRCP, and ERCP) compared with a conservative approach result in decreased

recurrent attacks of AP?

13. In patients undergoing ERCP, do patients who receive rectal indomethacin suppositories compared with patients who do not receive this therapy have a

decreased incidence of AP and severe AP?

14. In patients undergoing ERCP, do patients who receive intravenous hydration before the procedure compared with those who do not have extra hydration have

a decreased incidence of AP and severe AP?

15. In patients undergoing complex ERCP, does a pancreatic duct stent prevent AP compared with those who receive only rectal indomethacin suppositories?

16. In patients with idiopathic AP, does therapy directed at biliary disease, sphincterotomy, cholecystectomy, or oral ursodiol compared with conservative

management result in decreased recurrence of AP?

AP, acute pancreatitis; BUN, blood urea nitrogen; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; HCT,

hematocrit; ICU, intensive care unit; LOS, length of stay; MRCP, magnetic retrograde cholangiopancreatography; NPO, nothing by mouth; SIRS, systemic inflammatory

response syndrome.

important impact on the confidence in the estimate and would

Summary of evidence

likely affect the conclusions. Very low-quality evidence indicates

The diagnosis of AP most often is established by identification of 2 of

very little confidence in the effect estimate and that the true effect

the 3 following criteria: (i) abdominal pain consistent with the dis-

is likely to be substantially different from the estimate effect.

ease, (ii) serum amylase and/or lipase greater than 3 times the upper

Key concepts are statements that are not amenable to the

limit of normal, and/or (iii) characteristic findings from abdominal

GRADE process or when there are limitations in the available

imaging (5). Patients with AP typically present with epigastric or left

evidence from the literature but may be valuable to clinicians

upper quadrant pain. The pain is usually described as constant with

caring for patients with AP. In some instances, key concepts are

radiation to the back, chest, or flanks, but this description is non-

derived using a combination of extrapolation from the literature

specific. The intensity of the pain is usually described as severe but

and expert opinion. Key concepts are listed in Table 3.

can be variable. The intensity and location of the pain do not cor-

relate with severity. Pain described as dull, colicky, or located in the

lower abdominal region is not consistent with AP and suggests an

DIAGNOSIS

alternative etiology. Abdominal imaging is often helpful to determine

Key concepts

the diagnosis of AP in patients with atypical presentations. While the

laboratory diagnosis of AP has historically relied on elevations of the

1. We suggest that early/at admission routine computed tomography

amylase and lipase, many patients with AP are not correctly di-

(CT) not be performed for the purpose of determining severity in

agnosed (6). Due to limitations on sensitivity and negative predictive

AP and should be reserved for patients in whom the diagnosis is

value, serum amylase alone cannot be used reliably for the diagnosis

unclear or who fail to improve clinically within the first 48-72

of AP, and serum lipase is preferred.

hours after hospital admission and intravenous hydration.

Amylase in patients with AP generally rises within a few

hours after the onset of symptoms and returns to normal values

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values below the upper limit of normal. Serum amylase con-

Table 2. Recommendations on the management of AP

centrations may be normal in alcohol-induced AP and

hypertriglyceridemia. The serum amylase may be falsely ele-

Etiology

vated in conditions that cause hyperamylasemia other than

1. We suggest transabdominal

Conditional recommendation,

AP; for example, in macroamylasemia, a syndrome charac-

ultrasound in patients with AP to

very low quality of evidence

terized by the formation of large molecular complexes between

evaluate for biliary pancreatitis and a

amylase and abnormal immunoglobulins, in patients with a

repeat ultrasound if the initial

decreased glomerular filtration rate, in diseases of salivary

examination is inconclusive

glands, and in extrapancreatic abdominal diseases associated

2. In patients with IAP, we suggest

Conditional recommendation;

with inflammation, including acute appendicitis, cholecystitis,

additional diagnostic evaluation with

very low quality of evidence

intestinal obstruction or ischemia, peptic ulcer, and gyneco-

repeat abdominal ultrasound, MRI,

logical diseases (9).

and or endoscopic ultrasound

Serum lipase seems to be more specific and remains elevated

Initial management

longer than amylase following disease presentation. Despite

recommendations of recent classifications and guidelines (5,10)

3. We suggest moderately aggressive

Conditional recommendation,

that emphasize the advantage of serum lipase, similar problems

fluid resuscitation for patients with AP.

low quality of evidence

with the predictive value remain in certain patient populations.

Additional boluses will be needed if

Lipase is also found to be elevated in a variety of nonpancreatic

there is evidence of hypovolemia

diseases. For example, an upper limit of normal greater than 3-5

4. We suggest using lactated Ringer

Conditional recommendation,

times may be needed, especially in some patient groups such as

solution over normal saline for

low quality of evidence

diabetic patients (11,12). A Japanese consensus conference to

intravenous resuscitation in AP

determine appropriate cutoff values for amylase and lipase

ERCP in AP

could not reach consensus on appropriate upper limits of nor-

5. We suggest medical therapy over early

Conditional recommendation,

mal (13). Assays of many other pancreatic enzymes have been

(within the first 72 hr) ERCP in acute

low quality of evidence

assessed during the past 15 years, but none seem to offer better

biliary pancreatitis without cholangitis

diagnostic value than those of serum amylase and lipase (14).

Although most studies show a diagnostic efficacy of greater than

Preventing PEP

3-5 times the upper limit of normal, clinicians must consider the

6. We recommend rectal indomethacin

Strong recommendation,

clinical condition of the patient when evaluating amylase and

to prevent PEP in individuals

moderate quality of evidence

lipase elevations. When doubt about the diagnosis of AP exists,

considered to be at high risk of post-

abdominal imaging may assist. Once the diagnosis of AP is

ERCP pancreatitis

established, there is no reason to follow the serum amylase or

7. We suggest placement of a pancreatic

Conditional recommendation,

lipase because there is no relationship to severity, prognosis, or

duct stent in patients at high risk for

low quality of evidence

impact on a decision to refeed or discharge the patient (15).

PEP who are receiving rectal

While the diagnosis of AP is readily established with charac-

indomethacin

teristic pain, symptoms, and elevations of amylase and lipase

greater than 33 normal, some patients without AP will have

The role of antibiotics in AP

elevated amylase and/lipase, sometimes greater than 33 nor-

8. We suggest against prophylactic

Conditional recommendation,

mal. In the absence of abdominal pain consistent with the dis-

antibiotics in patients with severe AP

very low quality of evidence

ease, elevations of amylase and lipase do not predict the

9. We suggest against FNA in patients with

Conditional recommendation,

development of AP.

suspected infected pancreatic necrosis

very low quality of evidence

Abdominal imaging may prove useful to confirm the di-

Nutrition in AP

agnosis of AP. Contrast-enhanced CT provides more than

90% sensitivity and specificity for the diagnosis of AP (16).

10. In patients with mild AP, we suggest

Conditional recommendation,

Routine use of abdominal CT in patients with AP is un-

early oral feeding (within 24-48 hr)

low quality of evidence

warranted because the diagnosis is apparent in most patients

as tolerated by the patient compared

and most have a mild uncomplicated course. However, in a

with the traditional NPO approach

patient failing to improve after 48-72 hours (e.g., persistent

11. In patients with mild AP, we suggest

Conditional recommendation,

pain, fever, nausea, and unable to begin oral feeding), CT or

initial oral feeding with low-fat solid diet

low quality of evidence

magnetic resonance imaging (MRI) is recommended to assess

rather than a stepwise liquid to solid

local complications such as pancreatic necrosis (17-19). CT

approach

and MRI are comparable in the early assessment of AP (20).

AP, acute pancreatitis; ERCP, endoscopic retrograde

MRI, while more expensive, time-consuming, and challeng-

cholangiopancreatography; FNA, fine-needle aspiration; IAP, idiopathic AP;

ing in claustrophobic patients, has advantages in those with

NPO, nothing by mouth; PEP, post-ERCP pancreatitis.

contrast allergy and renal insufficiency (can diagnose ne-

crosis on nongadolinium T2-weighted images) and can more

accurately detect stones in common bile duct (CBD) and

pancreatic duct disruption. Newer techniques such as sub-

within 3-5 days; however, it may remain within the normal

traction CT and perfusion CT are reported to detect necrosis

range on admission in as many as one-fifth of patients (7,8).

earlier than conventional CT, but the techniques have not yet

Compared with lipase, serum amylase returns more quickly to

found wide acceptance.

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Table 3. Key concepts in AP

Key concepts

Diagnosis

1. We suggest that early/at admission routine CT not be performed for the purpose of determining severity in AP and should be reserved for patients in whom the

diagnosis is unclear or who fail to improve clinically within the first 48-72 hr after hospital admission

Etiology

2. In the absence of gallstones and/or significant history of alcohol use, serum triglyceride should be obtained and considered the etiology, preferably if greater

than 1,000 mg/dL

3. In patients older than 40 years in whom an etiology is not established, a pancreatic tumor should be considered as a possible cause of AP

4. Following a second episode of AP with no identifiable cause, in patients fit for surgery, we suggest performing a cholecystectomy to reduce the risk of recurrent

episodes of AP

Initial assessment and risk stratification

5. Hemodynamic status and risk assessment should be performed to stratify patients into higher-risk and lower-risk categories to assist consideration of

admission to a nonmonitored bed or monitored bed setting, including the intensive care setting

6. Patients with organ failure and/or the SIRS should preferably be admitted to a monitored bed setting

7. Scoring systems and imaging alone are not accurate in determining which patients with AP will develop moderately severe or severe AP

8. In patients with mild disease, clinicians should remain vigilant for the development of severe disease and organ failure during the initial

48 hr from admission

9. Risk factors for the development of severe disease (Table 4) include elevated BUN, HCT, the presence of obesity, comorbidities,

and the presence of SIRS

Initial management

10. While we suggest all patients with AP receive moderately aggressive intravenous hydration of isotonic crystalloid, caution is needed if a cardiovascular and/or

renal comorbidity exists. Patients should be monitored for volume overload

11. Fluid resuscitation in patients with AP is likely more important early in the course of the disease (within the first 24 hr)

12. Fluid volumes need to be reassessed at frequent intervals within 6 hr of presentation and for the next 24-48 hr with a goal to decrease the BUN

ERCP in AP

13. In patients with AP complicated by cholangitis, early ERCP within the first 24 hr has been shown to decrease morbidity and mortality

14. In the absence of cholangitis and/or jaundice, if a common bile duct stone is suspected, MRCP or EUS should be used to screen for the presence of common

bile duct stones before the use of ERCP, and diagnostic ERCP should be avoided

The role of antibiotics in AP

15. While antibiotics should not be used in patients with sterile necrosis, antibiotics are an important part of treatment in infected necrosis along with

debridement/necrosectomy

16. In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis should be used largely to delay surgical, endoscopic, and radiologic

drainage beyond 4 wk. Some patients may avoid drainage altogether because the infection may completely resolve with antibiotics

17. Routine administration of antifungal agents along with prophylactic or therapeutic antibiotics is not needed

Nutrition in AP

18. Enteral nutrition in patients with moderately severe or severe AP seems to prevent infectious complications

19. Parenteral nutrition should be avoided, unless the enteral route is not possible, not tolerated, or not meeting the caloric needs

20. Using a nasogastric rather than nasojejunal route for delivery of enteral feeding is preferred because of comparable safety and efficacy

The role of surgery in AP

21. Patients with mild acute biliary pancreatitis should undergo cholecystectomy early, preferably before discharge

22. Minimally invasive methods are preferred to open surgery for debridement and necrosectomy in stable patients with symptomatic

pancreatic necrosis

23. We suggest delaying any intervention (surgical, radiological, and/or endoscopic) in stable patients with pancreatic necrosis, preferably 4 wk, to allow for the

wall of collection to mature

AP, acute pancreatitis; BUN, blood urea nitrogen; CT, computed tomography; ERCP, endoscopic retrograde cholangiopancreatography; HCT, hematocrit; MRCP, magnetic

retrograde cholangiopancreatography; SIRS, systemic inflammatory response syndrome.

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ETIOLOGY OF AP

causative agents. A novel classification system recently published

Recommendations

can assist clinicians in determining the level of evidence that a

particular drug causes AP (34).

1. We suggest transabdominal ultrasound in patients with AP to

Primary and secondary hypertriglyceridemia can cause AP;

evaluate for biliary pancreatitis and a repeat US if the initial

however, these account for only 5% of all cases of AP, although

examination is inconclusive (conditional recommendation, very

may be higher and in up to 56% of AP in pregnancy (35). Serum

low quality of evidence).

TG should rise above 1,000 mg/dL to be considered the cause of

2. In patients with idiopathic AP (IAP), we recommend additional

AP (36,37). There is little information about the risk of AP due to

diagnostic evaluation with repeat abdominal ultrasound, MRI,

high TG at a population level. A sophisticated analysis suggested

and/or endoscopic ultrasound (EUS) (conditional

that the risk of AP increased by 4% for every 100 mg/dL of TG

recommendation; very low quality of evidence).

above the normal limit, even higher when TG levels are above 500

mg/dL (38). A lactescent serum has been observed in as many as

20% of patients with AP; therefore, a fasting TG level should be re-

Key concepts

evaluated 1 month after discharge when hypertriglyceridemia is

suspected (39).

2. In the absence of gallstones and/or a significant history of alcohol

A benign or malignant mass that obstructs the main pancre-

use, serum triglyceride (TG) should be obtained and considered

atic or biliary ducts can result in AP. It has been estimated that

the etiology, preferably if greater than 1,000 mg/dL.

5%-14% of patients with benign or malignant pancreatobiliary

3. In patients older than 40 years in whom an etiology is not

tumors present with acute idiopathic pancreatitis (40-42). Pan-

established, a pancreatic tumor should be considered as a

possible cause of AP.

creatic cancer should be suspected in any patient older than 40

years with idiopathic pancreatitis, especially with a prolonged or

4. Following a second episode of AP with no identifiable cause, in

patients fit for surgery, we suggest performing a cholecystectomy

recurrent course (43). A recent review reported that approxi-

to reduce the risk of recurrent episodes of AP.

mately 1% of AP was due to pancreatic cancer (44). Thus, a

contrast-enhanced CT scan with thin slices or MRI/magnetic

retrograde cholangiopancreatography (MRCP) is needed in these

Summary of evidence

patients. A more extensive evaluation including EUS and/or

Gallstones and alcohol. The etiology of AP can be readily

MRCP may be indicated initially or after a recurrent episode of

established in most patients. The most common causes include

IAP (45,46).

gallstones (40%-70%) and alcohol (25%-35%) (21-23). Due to its

Idiopathic and recurrent AP. IAP is defined as pancreatitis with

commonality and importance of preventing a recurrent attack,

no etiology established after initial laboratory (including lipid and

abdominal ultrasound to evaluate for cholelithiasis should be

calcium levels) and imaging tests (transabdominal ultrasound

performed on all patients with AP (24). A large retrospective

and MRCP in the appropriate patient) (47,48). In many patients,

study confirmed the high accuracy and sensitivity of ultrasound

an etiology may eventually be found, yet in some, no definite

to diagnose a biliary etiology for AP and found that accuracy was

cause is ever established. Patients with no obvious etiology should

even higher when a second ultrasound was repeated 1 week after

be referred for a repeat ultrasound and TG level as an outpatient

the initial study if the initial study was inconclusive (25). Iden-

because initial hospital evaluation often fails to identify gallstones

tification of gallstones as the etiology should prompt referral for

and/or elevated TG level (26,47). While EUS may be helpful in

cholecystectomy to prevent recurrent attacks and potential biliary

identifying an underlying etiology, routine endoscopic retrograde

sepsis (26,27). Gallstone pancreatitis is usually an acute event and

cholangiopancreatography (ERCP) should not be performed

cured when the stone is removed or passes. Depending on age and

because of the increased risks of causing pancreatitis.

comorbidities, patients who have undergone a biliary sphincter-

EUS has been widely studied as a modality for elucidating the

otomy should also be referred for cholecystectomy because they

etiology of IAP. In patients with recurrent IAP, EUS identifies the

remain at risk of recurrent disease (28).

etiology in most patients (49). In a prospective study evaluating

Alcohol-induced pancreatitis often manifests as a spectrum,

the role of EUS in AP, Yusoff et al (49) identified the etiology in

ranging from discrete episodes of AP to chronic irreversible

almost a third of patients after an initial attack of idiopathic

changes. The diagnosis should not be entertained unless a person

pancreatitis. When evaluating 34 studies evaluating the efficacy of

has consumed over 5 years moderate or heavy alcohol con-

EUS and MRCP, despite the superiority of EUS, the addition of

sumption (29). “Heavy” alcohol consumption is generally con-

MRCP seems complementary in the evaluation of IAP (50).

sidered to be greater than 50 g per day, but is likely much higher.

Even with a diagnosis established, a recurrent attack of AP is

Clinically evident AP occurs in only up to 5% of heavy drinkers;

seen in approximately 20%-29% patients after an initial attack of

thus, there are likely other factors that sensitize individuals to the

AP (27). Recurrent pancreatitis occurs more often in male indi-

effects of alcohol, such as genetic factors (30) and tobacco use

viduals, smokers, and those with alcohol with an etiology (51).

(23,27,31).

Recurrence of alcoholic AP is likely due to ongoing alcohol abuse.

Other etiologies of AP. In the absence of alcohol or gallstones,

Treatment has been shown to decrease recurrent disease and the

caution must be exercised when attributing a possible etiology for

development of chronic pancreatitis (27,29). In addition, failure

AP to another agent or condition. Medications, infectious agents,

to treat a biliary etiology, such as gallstones, is a common cause of

and metabolic causes such as hypercalcemia and hyper-

recurrent AP (52). It is important that clinicians treat these un-

triglyceridemia are rare causes, more often falsely attributed to

derlying etiologies to prevent recurrent disease and the de-

causing AP

(32,33). Whereas some drugs, such as

velopment of chronic pancreatitis.

mercaptopurine, azathioprine, and didanosine clearly can cause

There is growing evidence that gallstones or tiny gallstones

AP, there are limited data supporting most medications as

(microlithiasis and sludge) are the cause of IAP in most of whom

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424

Tenner et al

the etiology has not been identified (53,54). Despite extensive

Summary of evidence

evaluation, many patients with IAP will have no objective evi-

Definition of severe AP. Almost a third of patients with AP will

dence of gallstones, even microlithiasis (55). Stevens et al (54)

develop severe disease or moderately severe disease (65). Severe

retrospectively followed up 2,236 patients with IAP who did and

AP is defined by the presence of persistent organ failure (fails to

did not undergo cholecystectomy. They found a significant re-

resolve within 48 hours) and/or death (5). Organ failure is defined

duction in recurrent pancreatitis in those patients with normal

in simple clinical terms as shock (systolic blood pressure less than

gallbladders who underwent cholecystectomy. In a small ran-

90 mm Hg), pulmonary insufficiency (PaO₂ less than 60 mm Hg),

domized prospective trial in patients with idiopathic pancreatitis,

renal failure (creatinine .2 mg/dL after rehydration), and/or

laparoscopic cholecystectomy was found to be highly effective in

gastrointestinal bleeding (.500 mL/24 hours) or modified

preventing recurrent AP with a number needed to treat to prevent

Marshall score of 2 or more in the 3 accepted organ systems (5).

1 attack being 5 persons (56). Patients with IAP who have ab-

Moderately severe disease is defined as transient organ failure

normal LFT on the first day of their presentation may be more

(resolves within 48 hours) and/or the development of local

likely to benefit (57). A recent meta-analysis in patients with IAP

complications (acute pancreatic and/or peripancreatic fluid col-

after extensive testing including EUS and ERCP found signifi-

lections, acute necrotic collections, pseudocyst or walled-off

cantly fewer recurrences of AP after cholecystectomy, 11% vs 39%

pancreatic necrosis). While the above is a severity classification,

(58). Based on the available evidence, we conclude that following

the morphologic classification describes necrotizing AP (usually

an episode of AP with no identifiable cause, in patients who are

synonymous with moderately severe and severe disease) vs

surgical candidates, cholecystectomy should be performed to

interstitial/edematous AP (usually mild in severity). Pancreatic

reduce the risk of recurrent episodes of pancreatitis.

necrosis is defined as diffuse or focal areas of nonviable pancreatic

Anatomic and physiologic anomalies of the pancreas occur in

parenchyma greater than 3 cm in size or greater than 30% of

10%-15% of the population, including pancreas divisum and

the pancreas

(66). Necrotizing pancreatitis includes pure

sphincter of Oddi dysfunction (SOD) (59). It remains unclear

peripancreatic necrosis (approximately 45%), pancreatic and

whether these disorders cause AP (60). Endoscopic therapy, fo-

peripancreatic necrosis (approximately 45%), and rarely pure

cusing on treating pancreas divisum and/or SOD, carries a sig-

pancreatic necrosis (approximately 5%). Pancreatic necrosis can

nificant risk of precipitating AP and should be performed only in

be sterile or infected (discussed further). In the absence of pan-

specialized units (61). The landmark EPISOD trial ruled out the

creatic necrosis and/or organ failure, in mild disease, the edem-

role of endoscopic sphincterotomy in SOD type 2 and SOD type

atous pancreas is defined as interstitial pancreatitis. Although

3 (62).

there is some correlation between pancreatic necrosis, hospital

While the role of genetic defects contributing to this disorder

length of stay, and organ failure, patients with sterile necrosis and

has become increasingly recognized and may be a contributory

infected necrosis are as likely to have organ failure (67,68).

cause in patients with anatomic anomalies (63), it is not clear

Most episodes of AP are mild and self-limiting, needing only

how this can be used effectively in most patients with idiopathic

brief hospitalization. However, 20% of patients develop a moder-

pancreatitis. Genetic testing may be useful in patients with more

ately severe or severe disease requiring a prolonged hospitalization

than 1 family member with pancreatic disease (64). Patients

(69). Most patients with severe disease present to the emergency

with true recurrent IAP should be evaluated at centers of ex-

department with no organ failure or pancreatic necrosis. The fact

cellence focusing on pancreatic disease, providing advanced

that most patients who develop a complicated course initially

endoscopy, genetic testing, and a combined multidisciplinary

present to the emergency department appearing to have mild

approach.

disease, without organ failure or necrosis, has led clinical scientists

to recommend intensive early supportive care with aggressive or

moderately aggressive intravenous hydration (70,71).

INITIAL ASSESSMENT AND RISK STRATIFICATION

Predicting severe disease. Moderately severe and severe AP

Key concepts

constitute approximately 15%-25% of all cases of AP and prac-

tically account for all the morbidity and mortality of this disease.

5. Hemodynamic status and risk assessment should be performed

While a small proportion of patients with AP can be diagnosed as

to stratify patients into higher-risk and lower-risk categories to

assist consideration of admission to a nonmonitored bed or

moderately severe AP during the first 24 hours based on the

monitored bed setting, including the intensive care setting.

presence of any organ failure by accepted criteria and or (peri)

6. Patients with organ failure and/or the systemic inflammatory

necrotizing pancreatitis on CT scan, a substantial proportion of

response syndrome (SIRS) should preferably be admitted to a

patients cannot be reliably classified into mild, moderate, or se-

monitored bed setting.

vere during the first 24-48 hours and sometimes up to 72 or 96

7. Scoring systems and imaging alone are not accurate in

hours. This is the basis for several years of description of nu-

determining which patients with AP will develop moderately

merous clinical markers, laboratory markers, and or scoring

severe or severe AP.

systems to predict the future development of 1 of the 3 types

8. In patients with mild disease, clinicians should remain vigilant for

during the initial 24-48 hours. The main purpose of predicting or

the development of severe disease and organ failure during the

identifying those with increasing morbidity and mortality is to

initial 48 hours from admission.

triage them into high-level care and select them for newer

9. Risk factors of the development of severe disease (Table 4)

interventional trials such as drug trials (sparing patients with mild

include elevated blood urea nitrogen (BUN), hematocrit (HCT),

AP, who may not require such agents with the attendant side

the presence of obesity, comorbidities, and the presence of the

effects). However, the main problem with all the predicting

SIRS.

markers and systems is the inability to predict moderately severe

and severe types with high degree of accuracy. At best, 50% of the

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the use of accurate predicting tools, but such a study will be

Table 4. Clinical findings associated with a severe course for

clinically pertinent only if a drug or other specific therapy is

initial risk assessment^a

available to treat AP.

Elevated HCT ($44), BUN ($20 mg/dL), C-reactive protein

Patient characteristics

($150 mg/dL), and creatinine ($2 mg/dL) have been reported in

Age .55 (69,213)

numerous studies to have a significant predictive value for de-

Obesity (BMI .30 kg/m²) (93)

termining moderately severe and severe disease. Such elevated

Altered mental status (79,95)

values are based on the hemoconcentration, which occurs due to

multiple causes such as nausea and or vomiting, third-space

Comorbid disease (69)

losses, and others. There is one report of decreased hospital stay

The systemic inflammatory response syndrome (99,100)

when a paging system alert and a web-based instrument was

Defined by the presence of .2 of the following criteria:

available to the clinicians to treat AP, when compared with the

Pulse .90 beats per minute

outcomes from a historical control (78). In another study, a BUN

#22 mg/dL or falling BUN called for reducing the intravenous

Respirations .20 per minute or PaCO₂ ,32 mm Hg

fluids to 1.5 mL/kg per hour from 3 mL/kg per hour and if no such

Temperature .38 °C or .36 °C

reduction is observed, to re-bolus. The presence of organ failure,

WBC count .12,000 or ,4,000 cells/mm³ or .10% immature

SIRS, or Bedside Index for Severity Scoring System score of 3 or

neutrophils (bands)

more suggested to the treating physicians to consider intensive

care unit (ICU) treatment (79). While the study showed a re-

Laboratory findings

duction in the length of stay with this intervention, no effect on

BUN .20 (79,92)

other important outcomes was noted. In addition, it was also

Rising BUN (79,92)

difficult to assess which of the components of the intervention

HCT .44 (83)

contributed to the clinical outcome.

In a systematic review of randomized controlled trials (RCT)

Rising HCT (83)

on goal-directed intravenous hydration in AP, there was found to

Elevated creatinine (214)

be insufficient evidence to state that goal-directed therapy, using

Radiology findings

various parameters to guide fluid administration, reduces the risk

Pleural effusions (94)

of persistent single or multiple organ system failure, infected

pancreatic necrosis, or mortality from AP (77). The various pa-

Pulmonary infiltrates (69)

rameters that were described in those studies for goal-directed

Multiple or extensive extrapancreatic collections (16)

intravenous hydration included HCT, creatinine, BUN, and

AP, acute pancreatitis; BMI, body mass index; BUN, blood urea nitrogen; HCT,

others. Similarly, another systematic review found scant high-

hematocrit; WBC, white blood cell.

quality evidence for the numerous goal-directed methods or

^aThe presence of organ failure and/or pancreatic necrosis defines severe AP.

combinations (80).

AP is an unpredictable disease early in its course. Clinicians

must recognize the inability to predict the development of severe

cases predicted to be moderately severe or severe by any pre-

disease in patients presenting with AP within the first 24-48

dicting system turn out to be such cases, while the prediction for

hours after admission. Despite intense research, severity scoring

mild AP is highly reliable and only approximately 3% progress to

systems are cumbersome, typically require 48 hours to become

moderately severe or severe. Hence, currently, the systems are

accurate, and when predictive of severity, the patient’s condition

only useful to predict the mild type, which helps in earlier dis-

is obvious regardless of the score. This is especially true for the

charge of such patients. These limitations of all different type of

Ranson, Imrie, and APACHE scoring systems. The Bedside Index

predictors have been highlighted for the past few years (72,73).

for Severity Scoring System score, which includes BUN and the

Novel pathogenesis markers, next-generation genetic tests iden-

presence of SIRS, has been consistently shown to be superior but

tifying polymorphisms, and artificial intelligence analysis of large

may be no more accurate than simply monitoring patients for

repositories of data may identify effective predictors (74). An

both BUN and/or the development of SIRS (81,82).

expert review suggested that expert clinician judgment and sim-

Although numerous laboratory tests have been studied to

ple SIRS score is as good as any complex scoring system or any

predict severity in patients with AP (83-85), no single laboratory

other predictor (75). In a recent editorial, there was a plea to stop

test is consistently accurate to predict severity in patients with AP

looking for more predictors and instead focus on the etiology and

(86-88). Several investigators have found a rise in HCT and/or

pathogenesis of severe AP with a view to develop specific treat-

rising BUN at 24 hours to be a reliable test in predicting mortality

ments for AP (76).

and persisting multiorgan failure in patients with AP (83,84,89).

There have been no studies that looked at applying any of the

A rising BUN within the first 24 hours has been shown to be

predictors resulting in a clinical impact compared with routine

associated with increased morbidity and mortality in patients

care. The reason for this is mainly 2-fold: the inability of accurate

with AP (84). This is likely due to its indirect correlation with

prediction and the lack of specific treatment, besides supportive

decreased intravascular volume and decreased perfusion of the

care, to prevent severe disease. A recent technical review found no

pancreas.

studies using severity prediction tools to demonstrate an impact

While many studies, especially from Europe, have used the

on the clinical outcomes of AP using severity prediction tools

acute-phase reactant C-reactive protein to determine severity, it is

(77). The review recommended for future clinical trials there is a

not practical because it takes 48-72 hours to become accurate in

need for measuring clinical outcomes in groups with and without

predicting necrosis and/or death (90). By that time, most patients

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Tenner et al

have already developed obvious mild or severe disease. CT and/or

has been controversy over the timing, type, and degree of the

MRI also cannot reliably determine severity early in the course of

benefit of early hydration, there is a general consensus that

AP because necrosis usually is not present on admission and may

treating a patient with mild disease early in the course of the

develop after 24-48 hours (20,91). Thus, close examination to

disease with early aggressive or moderately aggressive hydration

assess early fluid losses, hypovolemic shock, and symptoms

is beneficial (71,111).

suggestive of organ dysfunction is crucial.

Patients with AP have marked systemic endothelial injury and

Rather than depending on a single laboratory test or scoring

increased vascular permeability leading to fluid shifts into the

system to predict the severity of AP, clinicians need to be aware of

interstitial space and peritoneum (112). This leads to decreased

the multiple risk factors of severe disease (Table 3). These include

intravascular volume. In addition to these third-space losses,

the following: the presence of SIRS (92), signs of hypovolemia,

patients presenting with AP are also hypovolemic due to vomit-

such as an elevated BUN (84) and an elevated HCT (83), obesity

ing, reduced oral intake, increased respiratory losses, and di-

(93), presence of pleural effusions and/or infiltrates (94), and

aphoresis. Direct evidence of hypoperfusion of the pancreas

altered mental status (95). The presence of SIRS at admission has

leading to cell death and necrosis has been shown (113). The

been found to be highly predictive of the development of organ

rationale for early intravenous hydration is based on the hy-

failure/severe disease (96).

pothesis that clinicians can reverse the decreased perfusion of the

During the early phase of the disease (within the first week),

pancreas from third-space losses and microangiopathic effects.

death occurs because of the development, persistence, and pro-

Intravenous hydration can promote blood flow preventing pan-

gressive nature of organ dysfunction (97,98). The development of

creatic cellular death, necrosis, and the ongoing release of pan-

organ failure seems to be related to the development and per-

creatic enzymes activating the numerous cascades characteristic

sistence of SIRS. The reversal of SIRS and early organ failure has

of pancreatic sepsis. In addition, intravenous hydration prevents

been shown to be important in preventing morbidity and mor-

the ongoing inflammation that leads to a cycle of increased vas-

tality in patients with AP (99-102). While the presence of SIRS

cular permeability leading to increased third-space fluid losses

during the initial 24 hours has a high sensitivity for predicting

and worsening the pancreatic hypoperfusion that leads to pan-

organ failure (85%) and mortality (100%), this finding lacks

creatic necrosis (Figure 1).

specificity for severe disease (41%). Clinicians need to recognize

While there is no marker for decreasing pancreatic perfusion,

that the presence at admission or early development of SIRS in a

the rise in BUN reflects decreased renal perfusion. This can be

patient with AP warrants aggressive hydration, support, and

interpreted as a marker for decreased pancreatic perfusion. In

monitoring. For this reason, such patients should be admitted to a

addition, as the intravascular fluid leaks to the peritoneum, the

monitored bed or, if organ failure is already present, the ICU as

HCT rises as hemoconcentration develops. Early intravenous

the outcome appears improved (103).

resuscitation is essential in correcting hypovolemia, supporting

the macrocirculation and microcirculation of the pancreas to

INITIAL MANAGEMENT

prevent serious complications such as pancreatic necrosis (114).

Recommendations

On an initial review of clinical trials, conflicting conclusions

may be found regarding the benefit of early aggressive in-

3. We suggest moderately aggressive fluid resuscitation for patients

travenous hydration. However, profound differences in study

with AP. Additional boluses will be needed if there is evidence of

design explain the findings. The negative studies typically en-

hypovolemia (conditional recommendation, low quality of

rolled only patients with severe disease and/or well beyond the

evidence).

time where early aggressive intravenous hydration would have

4. We suggest using lactated Ringer solution over normal saline for

been effective (115-117). While these studies raise concerns about

intravenous resuscitation in AP (conditional recommendation,

the continuous use of aggressive hydration beyond 48 hours, and

low quality of evidence).

in patients with severe disease, the role of early hydration (within

the first 6-12 hours) was not addressed in these negative studies.

In general, the human studies that enrolled patients with mild

Key concepts

disease and provided early aggressive intravenous hydration

within the first 24 hours have shown a benefit, decreasing both

10. While we suggest all patients with AP receive moderately

morbidity and mortality (3,110,118,119). When a benefit was not

aggressive intravenous hydration of isotonic crystalloid, caution

appreciated, there were too few patients included (low power) in

is needed if a cardiovascular and/or renal comorbidity exists.

the study and/or there was not a significant difference in the

Patients should be monitored for volume overload.

amount of fluids provided to the 2 groups during the first 24 hours

11. Fluid resuscitation in patients with AP is likely more important

(92,120).

early in the course of the disease (within the first 24 hours).

Lactated Ringer solution is preferred to normal saline in the

12. Fluid volumes need to be reassessed at frequent intervals within

resuscitation and early aggressive hydration of patients with AP.

6 hours of presentation and for the next 24-48 hours with a goal

to decrease the BUN.

The benefit of using lactated Ringer solution in large-volume

resuscitation has been shown in other disease states, leading to

better electrolyte balance and outcomes (121,122). Khatua et al

Summary of evidence

(123) found that lactated Ringer solution early benefits in sys-

The initial treatment of AP depends on intravenous hydration.

temic inflammation are by providing calcium that binds ionically

This recommendation is based on expert opinion (10,104), lab-

with nonesterified fatty acids that are associated with severe

oratory experiments

(105,106), clinical indirect evidence

disease in AP. Lactate has also been shown to reduce pancreatic

(83,84,107-109) epidemiologic studies (79), and both retro-

injury in AP by decreasing inflammation (124). There are addi-

spective and prospective clinical trials (3,53,92,110). While there

tional theoretical benefits to using the more pH-balanced lactated

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Management of Acute Pancreatitis

427

Figure 1. Role of moderately aggressive intravenous hydration in acute pancreatitis. Figure designed by Jasmine Saini, MD. BUN, blood urea nitrogen.

Ringer solution for fluid resuscitation compared with normal sa-

Monitoring patients with early aggressive intravenous hy-

line. Although both are isotonic crystalloid solutions, normal saline

dration depends on observation of clinical parameters such as

is more acidic with a pH of 5.5 and is associated with the de-

heart rate, blood pressure, and urine output. In general, in-

velopment of a nonanion gap hyperchloremic metabolic acidosis

travenous hydration providing for a decrease in the HCT (he-

and renal injury when large volumes are given (125). This has

modilution) and/or decreased BUN (increased renal perfusion)

relevance in AP where the process is premature trypsinogen acti-

have been shown to be associated with decreased morbidity and

vation that also requires a low pH. In addition, infusion of large

mortality (83,84). Although the precise timing of laboratory

volumes of normal saline has been associated with abdominal

testing and numbers for which the HCT and BUN should de-

discomfort in healthy volunteers. Thus, normal saline may exac-

crease have not been established, the latest evaluation should be

erbate the symptoms of abdominal pain associated with AP.

6-8 hours after admission (111). If an adjustment is to be made to

In 3 well-designed prospective randomized trials, lactated

the rate of hydration, it will need to be determined within this

Ringer solution has been shown to be more beneficial than nor-

time frame to assure the patient the benefit.

mal saline (53,92,119). Wu et al (92) found patients were less

A recent, elegant-designed, randomized prospective study by

likely to develop SIRS, a predictor of severe disease in patients

de-Madiera et al (116) has shown that moderate intravenous hy-

treated with lactated Ringer solution compared with those treated

dration the first 24-48 hours may be equally effective as aggressive

with normal saline. Lee et al (53) showed that patients who were

hydration. In this study, moderate hydration was less likely to cause

given lactated Ringer solution were less likely to be admitted to

volume overload when compared with early aggressive intravenous

the critical care unit and had a shorter hospitalization compared

hydration. From this study, we can conclude that in patients with

with patients with AP given normal saline. In patients who are in

no evidence of hypovolemia, an initial resuscitation rate of no more

the emergency department for a long period and inadequately

than 1.5 mL/kg of body weight per hour should be administered.

treated with early aggressive hydration, the benefit may not exist

However, in patients with hypovolemia, clinicians should admin-

and may be harmful when transferred to the floor or ICU (126).

ister a bolus of 10 mL/kg (71). While the presence of hypovolemia

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428

Tenner et al

might demand higher amounts and rates of hydration, most pa-

Summary of evidence

tients with AP will likely benefit from 3-4 L the first 24 hours,

The role of ERCP. The pathophysiology of gallstone pancreatitis

depending on body mass index. Close observation is ultimately the

involves the obstruction of the pancreatic duct by a gallstone that

key in managing patients with AP early in the course of the disease.

passes from the bile duct into the common channel as it opens

It is important to recognize that certain groups of patients, such as

into the duodenum. A persistent CBD stone (choledocholithiasis)

the older individuals and those with a history of cardiac and/or renal

can lead to persistent pancreatic duct and/or biliary tree ob-

disease, will need caution when applying hydration. Close moni-

struction, leading to necrosis and/or cholangitis (129). Although

toring for reported complications such as volume overload, pul-

intuitively, removal of obstructing gallstones from the biliary tree

monary edema, and abdominal compartment syndrome is needed

in patients with AP should reduce the complications, most gall-

(126,127). Use of central venous pressure measurement through a

stones readily pass to the duodenum and are lost in the stool

centrally placed catheter is commonly used to determine volume

(130). Most patients with gallstone pancreatitis will not benefit

status in this clinical setting. However, recent data indicate that the

from ERCP, including early ERCP.

intrathoracic blood volume index may have a better correlation with

Schepers et al (131) performed a multicenter trial to determine

cardiac index than central venous pressure, allowing more accurate

whether patients with gallstone pancreatitis and predicted severe

assessment of volume status for patients managed in the ICU.

AP (APACHE .8, Imrie .3, or C-reactive protein .150 mg/dL)

Once a patient has severe disease, there seems to be no benefit of

would benefit from early (within 24 hours) ERCP. Early ERCP

early aggressive hydration (115). Intravenous hydration in patients

was not found to decrease complications, including mortality in

with AP has been shown to be most effective early in the course of the

these patients. Yet, patients who underwent urgent ERCP were

disease (110). When severe disease develops and/or after 24 hours,

less likely to be readmitted for subsequent AP or cholangitis. The

aggressive hydration may actually be harmful (111,116,126,128).

authors concluded that urgent ERCP is indicated in this situation

While other experts and guidelines have advocated for using a term

only for cholangitis or progressive cholestasis defined by a rising

goal-directed hydration, clinicians often miss the goal failing to

bilirubin in the setting of severe or moderately severe AP (bili-

provide adequate hydration during the initial 24 hours when the

rubin .3-5 mg/dL).

moderately aggressive intravenous hydration is most important

(10,110). Keeping in mind that most patients with AP seem to have

PREVENTING POST-ERCP PANCREATITIS

mild disease, clinicians often do not appreciate the need to treat AP

Recommendations

with early hydration because the patients do not appear ill, often

having normal HCT and BUN. The goal in these patients seems to

6. We recommend rectal indomethacin to prevent post-ERCP

have been met. The problem is that AP results in an early extrava-

pancreatitis (PEP) in individuals considered to be at high risk of

sation of intravascular fluid into the peritoneum averaging 2-4 L

PEP (strong recommendation, moderate quality of evidence).

over the first 48 hours (109). If early moderately aggressive in-

7. We suggest placement of a pancreatic duct stent in patients at

travenous hydration is not provided to these patients with initially

high risk for PEP who are receiving rectal indomethacin

appearing mild AP and the disease progresses, because the BUN and/

(conditional recommendation, low quality of evidence).

or HCT rise during the first 24-36 hours, the goal is missed, and the

risk of necrosis and/or organ failure increase (108,109). Rather than

goal-directed therapy, the role of intravenous hydration is better

Summary of evidence

thought of as do not miss the goal therapy, that is, do not allow the

AP remains the most common complication of ERCP. The in-

BUN and HCT to rise within the first 24-48 hours and do not let

cidence of AP varies widely 1%-30%, depending on a variety of

SIRS and/or renal insufficiency to develop. Because once these de-

factors, including patient demographics, intraendoscopy proce-

velop, the goal of hydration was missed, and mild disease may be

dures performed, and whether the patient has received pro-

progressing to severe disease.

phylaxis (132-134). Although most patients with PEP have mild

disease, some patients have severe disease and a complicated

course, including death. There has been significant interest in

ERCP IN AP

identifying interventions that can reduce PEP.

Recommendations

In general, diagnostic ERCP should be avoided in most pa-

tients and, if needed, should be performed in Centers of Excel-

5. We suggest medical therapy over early (within the first 72 hours)

lence. Clinicians must recognize that the risk of PEP is greater in

ERCP in acute biliary pancreatitis without cholangitis (conditional

the patient with a normal caliber CBD and normal bilirubin (odds

recommendation, low quality of evidence).

ratio 3.4) when compared with a patient who is jaundiced with a

dilated CBD (odds ratio 0.2) (135). In these patients, noninvasive

MRCP or less-invasive EUS should be used because these

Key concepts

methods of evaluating the CBD are as accurate and pose no risk of

pancreatitis (136).

13. In patients with AP complicated by cholangitis, early ERCP

Interventions shown to prevent PEP include the following: (i)

within the first 24 hours has been shown to decrease morbidity

guidewire cannulation compared with contrast-guided cannula-

and mortality.

tion, (ii) pancreatic duct stents in the appropriate patient, (iii) rectal

14. In the absence of cholangitis and/or jaundice, if a CBD stone is

indomethacin suppositories, and (iv) preprocedure intravenous

suspected, MRCP or EUS should be used to screen for the

hydration (137). Guidewire cannulation, in which the bile duct and

presence of CBD stones before the use of ERCP, and diagnostic

pancreatic duct are cannulated by a guidewire inserted through a

ERCP should be avoided.

catheter (e.g., a sphincterotome), has been shown to decrease the

risk of pancreatitis (138). This is likely by avoiding hydrostatic

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429

injury, but other factors may be involved. Providing clarity, in a

indomethacin and periprocedural hydration should be used in all

recent systematic review involving 15 trials, avoiding cannulation

patients before ERCP (137).

with radiocontrast agents decreased the risk of AP in most trials.

Patients undergoing ERCP who are at high risk for PEP will

The use of guidewire cannulation compared with contrast-guided

likely benefit from both rectal indomethacin and a pancreatic duct

cannulation also seems to decrease the risk of severe AP and other

stent. While a large-scale multicenter RCT showed that patients

complications, including bleeding and perforation (139).

who received rectal indomethacin alone were less likely to develop

In the appropriate patients undergoing ERCP, such as those

pancreatitis following ERCP than patients who received both rectal

with an ampullary tumor undergoing snare resection and those

indomethacin in combination with a pancreatic duct stent (152), a

undergoing endoscopic sphincterotomy, the use of a pancreatic

well-designed NIH-sponsored multicenter trial recently showed

duct stent has been shown to decrease the risk of severe PEP.

the opposite results (153). In this large trial conducted at 20 centers

Prophylactic pancreatic duct stenting is a cost-effective strategy

in the USA and Canada, 1950 patients at high risk for PEP were

for the prevention of PEP for high-risk patients (140); higher

randomly assigned to receive rectal indomethacin alone or in

incidence of severe pancreatitis has been reported in patients with

combination with a pancreatic duct stent. Patients at high risk were

failed pancreatic duct stenting (141). Yet, it is recognized that

less likely to have PEP when provided both rectal indomethacin

pancreatic duct stenting is not always technically feasible with

and a pancreatic duct stent. Therefore, prophylactic pancreatic

reported failure rate ranging from 4% to 10% (141). In addition,

duct stent placement is generally recommended in addition to

these studies supporting stent placement were unblinded and

rectal indomethacin in select patients at high risk for PEP. How-

performed by highly skilled therapeutic endoscopist, thus in-

ever, recognizing that this study was performed at tertiary care

troducing bias in favor of stenting into the results. Of more im-

centers of expertise, clinicians need to recognize the possible dif-

portance, these studies were performed before the widespread use

ficulty of placing a pancreatic duct stent in all patients at high risk

of rectal indomethacin (see further).

for PEP. A case by case approach is needed.

Multiple studies have shown that a single dose of 100 mg of

rectal indomethacin before or immediately after ERCP will pre-

THE ROLE OF ANTIBIOTICS IN AP

vent PEP in patients at high risk (134,142,143). However, in a

Recommendations

consecutive series of high-risk and low-risk patients at a single

center, no benefit to periprocedural rectal indomethacin sup-

8. We suggest against prophylactic antibiotics in patients with severe

positories was observed (144). While the benefit may not have

AP (conditional recommendation, very low quality of evidence).

been observed because of the inclusion of many patients at low

9. We suggest against fine-needle aspiration (FNA) in patients with

risk, the number needed to treat low-risk patients to prevent AP

suspected infected pancreatic necrosis (conditional

and severe AP may be still within the cost-effective range. Thus,

recommendation, very low quality of evidence).

rectal indomethacin suppositories (100 mg) should be used in all

patients undergoing ERCP, unless contraindicated (137).

Key concepts

In addition to rectal indomethacin, the use of a periprocedural

hydration with lactated Ringer solution has been shown to prevent

15. While antibiotics should not be used in patients with sterile

AP (145-147). Buxbaum (147) found that no patients developed

necrosis, antibiotics are an important part of treatment in

PEP when provided lactated Ringer solution at 3 mL/kg/hr during

infected necrosis along with debridement/necrosectomy.

the ERCP, a 20 mL/kg bolus after the procedure, followed by an 8-

16. In patients with infected necrosis, antibiotics known to penetrate

hour infusion at 3 mL/kg/hr. Similarly, 2 other randomized con-

pancreatic necrosis should be used largely to delay surgical,

trolled clinical trials showed a benefit to periprocedural intravenous

endoscopic, and radiologic drainage beyond 4 weeks. Some

hydration. Park et al (148) in a prospective randomized multicenter

patients may avoid drainage altogether because the infection

clinical trial showed that lactated Ringer solution at rate of 3 mL/mg

may completely resolve with antibiotics.

during the procedure and then 20 mL/kg bolus after the procedure

17. Routine administration of antifungal agents along with

significantly decreased the risk of PEP in average-risk to high-risk

prophylactic or therapeutic antibiotics is not needed.

patients. Similarly, Choi et al (149) found vigorous periprocedural

intravenous hydration with lactated Ringer solution reduced the

incidence and severity of PEP in average-risk and high-risk cases.

Summary of evidence

While these studies show a benefit to periprocedural infusion

Infectious complications. Infectious complications are a major

of lactated Ringer solution, the timing and additional benefit of

cause of morbidity and mortality in patients with AP, including

rectal indomethacin remains controversial. Mok et al

(142)

cholangitis (154), urinary tract infections (155), infected pseu-

conducted a randomized, double-blinded, placebo-controlled

docysts (abscesses), fluid collections (156), and infected pancre-

trial on patients at high risk of PEP, the use of a liter of intravenous

atic necrosis. SIRS that develops early in the course of AP may be

lactated Ringer solution pre-procedure with 100 mg of rectal

indistinguishable from sepsis because of fever, tachycardia,

indomethacin led to a significant decrease in postprocedure

tachypnea, and leukocytosis. When an infection is suspected,

pancreatitis. However, a larger volume of fluid and ongoing ag-

antibiotics should be given while the source of the infection is

gressive hydration post-ERCP has been shown to be not effective

being confirmed. However, once blood and other cultures are

in reducing PEP when rectal indomethacin suppositories are also

found to be negative, when no source of infection is identified,

used (150). Despite the evidence of the benefit of using rectal

antibiotics should be discontinued.

indomethacin suppositories, in a large study of more than 30,000

Sterile necrosis. The paradigm shift and controversy of using

patients, only one-third of patients were provided this method

antibiotics in AP has centered on pancreatic necrosis. When

of prophylaxis (151). When considering the costs, risks, and

compared with patients with sterile necrosis, patients with

potential benefits in light of the published literature, rectal

infected pancreatic necrosis have a higher mortality rate (mean

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430

Tenner et al

30%, range 14%-69%) (69). For this reason, preventing infection

is suspected. An immediate review of the Gram stain will often

of pancreatic necrosis is important. While some investigators

establish a diagnosis. However, it may be prudent to begin anti-

found that infection is rare in the first week after the onset of AP

biotics while awaiting microbiologic confirmation. If culture re-

(157), others have found that as many as 25% of all patients with

ports are negative, the antibiotics can be discontinued.

infected necrosis developed the infection in the first week (158).

There is some controversy as to whether a CT-FNA is necessary

Hypotension, early in the course of AP, has been believed to lead

in all patients. In many patients, the CT-FNA would not influence

to ischemia of the bowel and allow bacterial translocation from

the management of a patient (174). Many patients with sterile or

the colon leading to infection of necrosis (159). Alternatively, line

infected necrosis either improve quickly or become unstable, and

infections occurring after the first week have also been shown to

decisions on surgical intervention will not be influenced by the

lead to infection of necrosis (160).

results of the aspiration. In addition, antibiotics can be started for

Although early unblinded trials suggested a benefit in providing

suspected infection on clinical grounds even without the FNA of

antibiotics to patients with sterile necrosis by preventing infectious

the pancreatic necrosis because a negative aspiration would still

complications (155,161,162), subsequent better-designed trials have

make the antibiotic use necessary due to clinical suspicion (175). In

consistently failed to show a benefit (163-166). There have been 11

proven infection by blood or other body fluid cultures or by the

prospective randomized trials of evaluating the use of prophylactic

presence of gas in the pancreatic necrosis, the need for antibiotics is

antibiotics in severe AP, with rigorous study design, participants, and

clear. Because the infection will likely seed the necrosis, and the

outcome measures since 1993. Similarly, there were 10 meta-analyses

necrosis will be difficult to penetrate, antibiotics chosen should be

reported since 2006 describing the abovementioned RCT, although

known to penetrate the necrosis, such as carbapenems, quinolones,

the number of RCT in each meta-analysis varied depending on the

cephalosporins, and metronidazole (67,155,160,161). Routine

year of publication of meta-analysis and the selection criteria used for

administration of antifungal agents along with prophylactic or

choosing the RCT in each meta-analysis. Of interest, earlier meta-

therapeutic antibiotics is also not needed.

analyses and RCT reported a benefit with prophylactic antibiotic use

in terms of mortality, infection of pancreatic necrosis, and extrap-

NUTRITION IN AP

ancreatic infections; however, all the 3 placebo-controlled, double-

Recommendations

blind RCT, 5 of the 9 meta-analyses published after 2006, and 2 of the

recent guidelines (British Society of Gastroenterology and ACG

10. In patients with mild AP, we suggest early oral feeding (within

guidelines) (104,167) did not recommend the use of prophylactic

24-48 hours) as tolerated by the patient compared with the

antibiotics because of lack of benefit in the abovementioned

traditional nothing-by-mouth approach (conditional

outcomes.

recommendation, low quality of evidence).

Infected necrosis. The role of antibiotics in patients with necro-

11. In patients with mild AP, we suggest initial oral feeding with low-

tizing AP now focuses on the presence of infection. The concept

fat solid diet rather than a stepwise liquid to solid approach

(conditional recommendation, low quality of evidence).

that infected pancreatic necrosis requires prompt surgical de-

bridement has also been challenged by multiple reports and case

series showing that antibiotics alone can lead to resolution of in-

Key concepts

fection and, in select patients, avoid surgery altogether (168-170).

Pooling 11 studies that include 1,136 patients, there is a significant

18. Enteral nutrition in patients with moderately severe or severe AP

correlation between the timing of surgery and mortality. In general,

seems to prevent infectious complications.

in clinically stable patients, it seems that postponing necrosectomy

19. Parenteral nutrition should be avoided, unless the enteral route

in stable patients with antibiotics until 30 days after initial hospital

is not possible, not tolerated, or not meeting the caloric needs.

admission is associated with a decreased mortality.

20. Using a nasogastric rather than nasojejunal route for delivery of

Current consensus is that surgery should be performed on

enteral feeding is preferred because of comparable safety and

clinically unstable patients with infected necrosis. However, in

efficacy.

most patients, those clinically stable, the initial management of

infected necrosis should be a 30-day course of antibiotics before

surgery to allow the inflammatory reaction to become better or-

Summary of evidence

ganized (171). At this time, for a necrotic collection with a well-

Nutrition in mild AP. The long-held opinion that patients with AP

defined wall and liquefied material within, the decision and

should be nothing by mouth was based on the experience from other

method of drainage can be considered, including endoscopic,

acute abdominal conditions. The idea was to avoid food-induced

radiologic, and/or surgical intervention. If there is no response to

stimulation of pancreatic exocrine function, to decrease in-

such antibiotics in a short time or if the clinical situation deteri-

flammation and hasten recovery, and to place the pancreas at rest.

orates, necrosectomy/debridement should be performed. The

The historical practice was to wait until pain is minimal and enzymes

concept that urgent surgery is required in all patients found to

normalize or trend downward before oral feeding can be started. Oral

have infected necrosis is no longer valid.

feeding was gradually increased from clear liquid diet to soft and then

The role of CT-guided FNA. The technique of CT-guided FNA

to low-fat solid diet before discharge. It has been subsequently rec-

(CT-FNA) has proven to be safe, effective, and accurate in dis-

ognized that oral feeding maintains gut mucosal integrity and pre-

tinguishing infected and sterile necrosis (172,173). Because patients

vents translocation of bacteria from the gut lumen into the inflamed/

with infected necrosis and sterile necrosis may appear similar with

necrosed pancreatic tissue, predisposing to the serious complication

leukocytosis and fever and organ failure (67,68) it is impossible to

of infected pancreatic necrosis. This led to the concept of gut rousing

separate these entities without CT-FNA. Because the role of anti-

as opposed to gut resting (176).

biotics is best established in clinically proven infection, CT-FNA

Interest developed in early oral feeding (immediate or within

should be considered when pancreatic or extrapancreatic infection

24, 48, or 72 hours after admission) without waiting for the pain

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Management of Acute Pancreatitis

431

and pancreatic enzymes to normalize (177-183). While most of

important in patients with AP, especially in the intensive care

these studies were conducted in patients when the treating team

setting. Nasojejunal tube placement requires interventional ra-

allowed the patients to start oral feeding, some studies applied a

diology or endoscopy and thus can be expensive. For these rea-

novel approach of starting the feeds based on hunger experienced

sons, nasogastric tube feeding maybe preferred (195).

by patients. The results of this approach seem identical

The timing of initiating enteral feeding in patients with severe

(181,184,185). For such early feeding, it is important to have

disease is controversial. While studies initially suggested a benefit

bowel sounds present and no significant nausea, vomiting, or

in preventing infectious complications, more recent studies

ileus. While most of these studies were performed in cases with

suggest that early (within the first 24 hours) initiation of enteral

mild AP, there were some studies performed in both cases with

feeding is not beneficial. Bakker et al performed a large ran-

moderately severe and severe types of disease showing a benefit to

domized trial in patients with predicted severe AP (196) and

early oral feeding (181,185,186).

found that early enteral tube feeding within 24 hours did not

Systematic reviews and meta-analyses of RCT have highlighted

reduce the rate of infection (25% vs 26%) when compared with

the benefit of early oral feeding in patients with mild, moderately

on-demand feeding. In addition, early enteral tube feeding did

severe, and severe types of AP, without the need to advance the diet

not reduce mortality (11% vs 7%).

slowly from clear liquids to solids (187,188). The universal finding

in these studies demonstrate the safety of initiating early oral

THE ROLE OF SURGERY IN AP

feeding in mild and moderately severe AP without any increase in

important clinical outcomes, such as the development of necrosis,

Key concepts

organ failure, and/or other local complications. Such an approach

is beneficial by reducing the time to initiate solid feedings, thus

21. Patients with mild acute biliary pancreatitis should undergo

reducing the hospital stay and costs. In mild AP, oral intake should,

cholecystectomy early, preferably before discharge.

in general, be restored quickly. A low-fat solid diet has been shown

22. Minimally invasive methods are preferred to open surgery for

to be safe compared with clear liquids, providing more calories

debridement and necrosectomy in stable patients with

(178). Similarly, in other randomized trials, oral feeding with a soft

symptomatic pancreatic necrosis.

diet has been found to be safe compared with clear liquids and

23. We suggest delaying any intervention (surgical, radiological,

shorten the hospital stay (189,190). A desire for food, simple

and/or endoscopic) in stable patients with pancreatic necrosis,

preferably 4 weeks, to allow for the wall of collection to mature.

hunger, can help guide clinicians’ decision when to start feedings

(185). Based on these studies, oral feedings introduced in patients

with mild AP do not need to begin with clear liquids and increase in

a stepwise manner but may begin as a low-residue, low-fat, soft diet.

Summary of evidence

However, clinicians should be aware that discharging a patient with

Cholecystectomy. In patients with mild gallstone pancreatitis,

persistent nausea despite early eating can result in readmission for

same-admission cholecystectomy has been shown to decrease

recurrent AP (191).

recurrent gallstone-related complications, with a very low risk of

Nutrition in those with moderately severe and severe AP. There

cholecystectomy-related complications (198). When evaluating

is compelling data that patients with sepsis, in general, benefit from

the literature, including 8 cohort studies and 1 randomized trial

early refeeding (192). In general, parenteral nutrition should be

describing 998 patients who were discharged rather than undergo

avoided. There have been multiple randomized trials showing that

cholecystectomy compared with early cholecystectomy, 95 (18%)

TPN is associated with infectious and other line-related compli-

were readmitted for recurrent biliary events (18% vs 0%, P ,

cations (69). Because enteral feeding maintains and prevents dis-

0.0001), including recurrent biliary pancreatitis (n 5 43, 8%)

ruption of the gut mucosal barrier, prevents disruption, and

(197). Many of these patients experienced severe disease. In ad-

prevents the translocation of bacteria that seed pancreatic necrosis,

dition to a benefit in morbidity, same-admission cholecystectomy

enteral nutrition should be begun in patients with severe AP, es-

results in substantial cost savings to the health care system (199).

pecially pancreatic necrosis (175,193). A meta-analysis of 8 ran-

Patients with pancreatic necrosis complicating biliary pan-

domized controlled clinical trials involving 381 patients found a

creatitis will require complex decision-making between the sur-

decrease in infectious complications, organ failure, and mortality in

geon and gastroenterologist. In these patients, cholecystectomy is

patients with severe AP provided enteral nutrition compared with

typically delayed to a later course in the typically prolonged

those given TPN (193). If enteral nutrition is administered by tube

hospitalization, as part of the management of the pancreatic ne-

feeds, continuous infusion is preferred over cyclic or bolus ad-

crosis if present and/or to a later date after discharge (200).

ministration (192). In addition, a small peptide-based medium-

In most patients with gallstone pancreatitis, the CBD stone

chain TG oil formula may improve tolerance (193).

passes to the duodenum. Routine ERCP is not appropriate unless

Although the use of a nasojejunal route was preferred to avoid

there is a high suspicion of a persistent CBD stone, manifested by

the gastric phase of stimulation, nasogastric enteral nutrition

an elevation in the bilirubin (201,202). Patients with mild AP,

seems safe. A systematic review describing 92 patients from 4

whose bilirubin is normal, can undergo laparoscopic cholecys-

studies on nasogastric tube feeding found that nasogastric feeding

tectomy with intraoperative cholangiography, and any remaining

was safe and well tolerated in patients with predicted severe AP

bile duct stones can be dealt with by postoperative or intra-

(194). There have been some reports of a slight increase in the risk

operative ERCP. In patients with low to moderate risk, MRCP can

of aspiration with nasogastric feeding. These patients should be

be used preoperatively; however, routine use of MRCP is un-

placed in a more upright position and be placed on aspiration

necessary. In patients with mild AP who cannot undergo surgery,

precautions. Evaluating for residuals, retained volume in the

such as older individuals and/or those with severe comorbid

stomach, is not likely to be helpful. Compared with nasojejunal

disease, biliary sphincterotomy has been shown to be effective to

feeding, nasogastric tube placement is far easier, which is

prevent recurrent biliary AP (69).

The American Journal of GASTROENTEROLOGY

432

Tenner et al

laparoscopic surgery, radiologic catheter drainage, and endoscopy

are increasingly becoming the more common approaches. Although

these guidelines cannot discuss in detail the methods of debridement

nor the comparative effectiveness of each, due to limitations in data

and focus of this review, several generalizations are important.

In general, regardless of the method, minimally invasive ap-

proaches require the pancreatic necrosis to become better orga-

nized (171,204,206,207). Whereas early in the course of the

disease (within the first 7-10 days), pancreatic necrosis is a diffuse

solid and/or semisolid inflammatory mass, after 4 weeks, a fibrous

wall develops around the necrosis, which makes removal more

amenable to surgery, laparoscopic surgery, radiologic catheter

drainage, and/or endoscopic drainage.

Sometimes, these modalities can be combined. A well-

designed study from the Netherlands using a step-up approach

(percutaneous catheter drainage followed by video-assisted ret-

Figure 2. Late management of patients with AP. AP, acute pancreatitis; CT,

roperitoneal debridement) demonstrated the superiority of the

computed tomography; SIRS, systemic inflammatory response syndrome.

step-up approach by way of lower morbidity (less multiple organ

failure and surgical complications) and lower costs (207). The

Debridement of necrosis. Historically, open necrosectomy/

investigators confirmed a higher mortality with open surgery

debridement was the choice of treatment for infected necrosis

both as an emergency (78%) and planned (30%) compared with a

and symptomatic sterile necrosis. Decades ago, patients with

minimally invasive approach.

sterile necrosis underwent early debridement resulting in in-

Percutaneous drainage without necrosectomy may be the most

creased mortality. For this reason, early open debridement for

frequent minimally invasive method (208). The overall success

sterile necrosis was abandoned (87). For patients with infected

seems to be approximately 50% in avoiding surgery. Endoscopic

necrosis, it was falsely believed that mortality of infected necrosis

drainage of necrotic collections and later direct endoscopic

was nearly 100% if debridement was not performed urgently

necrosectomy have been reported in several large series. Two recent

(69,203). In a retrospective review of 53 patients where the me-

large multicenter studies (German and American) described the

dian time to surgery was 28 days, when necrosectomy for infected

results of direct endoscopic necrosectomy. In this endoscopic ap-

necrosis was delayed, mortality decreased 22% (157). After

proach, where endoscope is introduced into the necrotic cavity

reviewing 11 studies that included 1,136 patients, the authors also

typically through the gastric wall and necrotic tissue is removed

found a significant correlation between the timing of surgery and

under direct vision, results have been comparable (209,210). In a

mortality. It seems that postponing necrosectomy in stable pa-

recent well-designed randomized controlled clinical trial, endoscopic

tients with antibiotics until 30 days after initial hospital admission

necrosectomy seems to be superior to surgical necrosectomy (211).

is associated with a decreased mortality (168).

Regardless of the method, it must be remembered that many

The concept that infected pancreatic necrosis requires prompt

patients with sterile necrosis, and select patients with infected

surgical debridement has also been challenged by multiple reports

necrosis, seem to improve and remain asymptomatic, and no

and case series showing that antibiotics alone can lead to resolution

intervention may be necessary (212). The management of pa-

of infection and, in select patients, avoid surgery altogether

tients with necrosis is therefore very individualized, requiring

(204,205). In one report (170), of 28 patients given antibiotics for

consideration of both the clinical appearance of patients and the

the management of infected pancreatic necrosis, 16 patients avoi-

expertise available at the institution. Referral to centers of ex-

ded surgery. There were 2 deaths in the patients who underwent

pertise is of paramount importance because delaying intervention

surgery and 2 deaths in the patients who were treated with anti-

with maximal supportive care and using a minimally invasive

biotics alone. Thus, in this report, more than half the patients were

approach have both shown to be of benefit in reducing morbidity

successfully treated with antibiotics, and the mortality rates in both

and mortality in patients with acute necrotizing pancreatitis.

the surgical and nonsurgical groups were similar.

Current consensus is that the initial management of infected

ACKNOWLEDGEMENTS

necrosis for patients who are clinically stable should be a 2- to 4-

This guideline was produced in collaboration with the Practice

week course of antibiotics before surgery to allow the in-

Parameters Committee of the American College of Gastroenterology.

flammatory reaction to become better organized (171). At this

We thank our librarian Jen de Richemond for assistance in our

time, in a collection with a well-defined wall and liquefied ma-

literature search. We also give a special thanks to Jasmine Saini, MD,

terial within, the decision and method of drainage can be con-

who assisted in the research and design of the figures and collection of

sidered. For patients with symptomatic walled off pancreatic

many of the manuscripts reviewed.

necrosis, a combined multimodality approach bringing together

both minimally invasive surgery with endoscopic drainage seems

to be more effective, safer and results in a shorter hospitalization

CONFLICTS OF INTEREST

(168,203,204). Although further study is needed, the concept that

Guarantor of the article: Scott Tenner, MD, MPH, JD, FACG.

urgent surgery is required in patients found to have infected

Specific author contributions: All authors contributed to the

necrosis is no longer valid (Figure 2).

planning, data analysis, writing, and final revision of the manuscript.

Minimally invasive management of pancreatic necrosis. Mini-

Financial support: None to report.

mally invasive approaches to pancreatic necrosectomy including

Potential competing interests: None to report.

The American Journal of GASTROENTEROLOGY

VOLUME 119 | MARCH 2024 www.amjgastro.com

Management of Acute Pancreatitis

433

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The American Journal of GASTROENTEROLOGY

Gastroenterology 2024;166:521-532

CLINICAL PRACTICE UPDATES

AGA Clinical Practice Update on Diet and Nutritional Therapies in

Patients With Inflammatory Bowel Disease: Expert Review

Jana G. Hashash,¹ Jaclyn Elkins,² James D. Lewis,³ and David G. Binion⁴

¹Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida;²Department of Nutrition, Mayo Clinic,

Jacksonville, Florida;³Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania,

Philadelphia, Pennsylvania; and⁴Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh,

Pennsylvania

DESCRIPTION: Diet plays a critical role in human health, but

consistently been found to decrease the rate of flares in adults

especially for patients with inflammatory bowel disease (IBD).

with IBD. A diet low in red and processed meat may reduce

Guidance about diet for patients with IBD are often contro-

ulcerative colitis flares, but has not been found to reduce

versial and a source of uncertainty for many physicians and

relapse in Crohn’s disease. BEST PRACTICE ADVICE 2: Pa-

patients. The role of diet has been investigated as a risk factor

tients with IBD who have symptomatic intestinal strictures may

for IBD etiopathogenesis and as a therapy for active disease.

not tolerate fibrous, plant-based foods (ie, raw fruits and veg-

Dietary restrictions, along with the clinical complications of

etables) due to their texture. An emphasis on careful chewing

IBD, can result in malnutrition, an underrecognized condition

and cooking and processing of fruits and vegetables to a soft,

among this patient population. The aim of this American

less fibrinous consistency may help patients with IBD who have

Gastroenterological Association (AGA) Clinical Practice Update

concomitant intestinal strictures incorporate a wider variety of

(CPU) is to provide best practice advice statements, primarily

plant-based foods and fiber in their diets. BEST PRACTICE

to clinical gastroenterologists, covering the topics of diet and

ADVICE 3: Exclusive enteral nutrition using liquid nutrition

nutritional therapies in the management of IBD, while empha-

formulations is an effective therapy for induction of clinical

sizing identification and treatment of malnutrition in these

remission and endoscopic response in Crohn’s disease, with

patients. We provide guidance for tailored dietary approaches

stronger evidence in children than adults. Exclusive enteral

during IBD remission, active disease, and intestinal failure. A

nutrition may be considered as a steroid-sparing bridge ther-

healthy Mediterranean diet will benefit patients with IBD, but

apy for patients with Crohn’s disease. BEST PRACTICE ADVICE

may require accommodations for food texture in the setting of

4: Crohn’s disease exclusion diet, a type of partial enteral

intestinal strictures or obstructions. New data in Crohn’s dis-

nutrition therapy, may be an effective therapy for induction of

ease supports the use of enteral liquid nutrition to help induce

clinical remission and endoscopic response in mild to moderate

remission and correct malnutrition in patients heading for

Crohn’s disease of relatively short duration. BEST PRACTICE

surgery. Parenteral nutrition plays a critical role in patients

ADVICE 5: Exclusive enteral nutrition may be an effective

with IBD facing acute and/or chronic intestinal failure. Regis-

therapy in malnourished patients before undergoing elective

tered dietitians are an essential part of the interdisciplinary

surgery for Crohn’s disease to optimize nutritional status and

team approach for optimal nutrition assessment and manage-

reduce postoperative complications. BEST PRACTICE ADVICE

ment in the patient population with IBD. METHODS: This

6: In patients with IBD who have an intra-abdominal abscess

expert review was commissioned and approved by the AGA

and/or phlegmonous inflammation that limits ability to achieve

Clinical Practice Updates Committee and the AGA Governing

optimal nutrition via the digestive tract, short-term parenteral

Board to provide timely guidance on a topic of high clinical

nutrition may be used to provide bowel rest in the preoperative

importance to the AGA membership and underwent internal

phase to decrease infection and inflammation as a bridge to

peer review by the CPU Committee and external peer review

definitive surgical management and to optimize surgical out-

through standard procedures of Gastroenterology. The best

comes. BEST PRACTICE ADVICE 7: We suggest the use of

practice advice statements were drawn from reviewing existing

parenteral nutrition for high-output gastrointestinal fistula,

literature combined with expert opinion to provide practical

prolonged ileus, short bowel syndrome, and for patients with

advice on the role of diet and nutritional therapies in patients

IBD with severe malnutrition when oral and enteral nutrition

with IBD. Because this was not a systematic review, formal

has been trialed and failed or when enteral access is not

rating of the quality of evidence or strength of the presented

feasible or contraindicated. BEST PRACTICE ADVICE 8: In

considerations was not performed.

patients with IBD and short bowel syndrome, long-term

parenteral nutrition should be transitioned to customized hy-

dration management (ie, intravenous electrolyte support and/

BEST PRACTICE ADVICE STATEMENTS

or oral rehydration solutions) and oral intake whenever

possible to decrease the risk of developing long-term compli-

BEST PRACTICE ADVICE 1: Unless there is a contraindication,

cations. Treatment with glucagon-like peptide-2 agonists can

all patients with IBD should be advised to follow a Mediterra-

facilitate this transition. BEST PRACTICE ADVICE 9: All pa-

nean diet rich in a variety of fresh fruits and vegetables,

tients with IBD warrant regular screening for malnutrition by

monounsaturated fats, complex carbohydrates, and lean pro-

their provider by means of assessing signs and symptoms,

teins and low in ultraprocessed foods, added sugar, and salt for

including unintended weight loss, edema and fluid retention,

their overall health and general well-being. No diet has

and fat and muscle mass loss. When observed, more complete

522

Hashash et al

Gastroenterology Vol. 166, Iss. 3

evaluation for malnutrition by a registered dietitian is indi-

vegetables, for IBD management is a substantial revision

cated. Serum proteins are no longer recommended for the

from past instructions (Figure 1, Table 1). Prior emphasis on

identification and diagnosis of malnutrition due to their lack of

a low-residue, low-fiber diet is reasonable for patients with

specificity for nutritional status and high sensitivity to inflam-

IBD who are experiencing symptomatic disease flares and

mation. BEST PRACTICE ADVICE 10: All patients with IBD

worsening abdominal symptoms, but whenever possible,

should be monitored for vitamin D and iron deficiency. Patients

long-term IBD management should attempt to reintroduce

with extensive ileal disease or prior ileal surgery (resection or

fresh fruits, vegetables, and fiber (preferably soluble fiber).

ileal pouch) should be monitored for vitamin B12 deficiency.

Recent prospective, randomized, short-term (6-12 weeks)

BEST PRACTICE ADVICE 11: All outpatients and inpatients

studies have suggested that a Mediterranean diet and a

with complicated IBD warrant co-management with a regis-

more structured specific carbohydrate diet were equally

tered dietitian, especially those who have malnutrition, short

effective in achieving symptomatic remission and calpro-

bowel syndrome, enterocutaneous fistula, and/or are requiring

tectin response (Table 1).¹ Importantly, the use of a Medi-

more complex nutrition therapies (eg, parenteral nutrition,

terranean diet may mechanistically improve the diversity of

enteral nutrition, or exclusive enteral nutrition), or those on a

the gut microbiome and metabolome and hold additional

Crohn’s disease exclusion diet. We suggest that all newly

long-term health benefits, such as reduction of cardiovas-

diagnosed patients with IBD have access to a registered dieti-

cular disease, metabolic syndrome, and cancer. An inde-

tian. BEST PRACTICE ADVICE 12: Breastfeeding is associated

with a lower risk for diagnosis of IBD during childhood. A

pendent validation of the efficacy of the Mediterranean diet

healthy, balanced, Mediterranean diet rich in a variety of fruits

for patients with IBD was performed by Chicco et al.²

and vegetables and decreased intake of ultraprocessed foods

Nutritional counseling was provided to 142 patients with

have been associated with a lower risk of developing IBD.

IBD. After 6 months, both patients with UC and patients with

CD adhering to the Mediterranean diet had lower rates of

active disease, inflammatory biomarker elevation, and

Keywords: IBD; Nutrition; Diet; CDED; Parenteral Nutrition.

improved quality of life.

To date, there is no consistent evidence supporting the

avoidance of gluten in patients with IBD in the absence of a

he central purpose of the gastrointestinal tract is

celiac disease diagnosis or suspected gluten sensitivity.

nutrition, and this essential function is often

Although the use of a low fermentable oligo-, di-, and

compromised in patients with inflammatory bowel disease

monosaccharide and polyols (FODMAP) diet was found to

(IBD). There is growing recognition of the role of diet in the

improve symptoms in patients with IBD in a prospective,

care of patients with IBD, as both an etiopathogenic risk factor

randomized trial, this may be accompanied by potential

and, more recently, as a disease-modifying modality. Histori-

negative long-term consequences.³ The low-FODMAP diet

cally, there was limited guidance regarding diet for patients

results in the reduction of certain fecal microbiome organ-

with IBD. Other than to counsel on avoiding foods that worsen

isms and reduced generation of the short-chain fatty acid

symptoms and to avoid foods that may predispose to

butyrate, a key nutrient for gut epithelial health. Research

obstruction in those with strictures, health care providers had

has found that the organisms that are diminished in patients

limited diet-related input to give their patients. Although such

on a low-FODMAP diet tend to be associated with endo-

dietary advice may help improve symptoms in the acute

scopic and clinical remission when found in abundance,

setting, these approaches frequently led patients with IBD to

raising concern about the long-term effects of low-FODMAP

avoid what are traditionally considered healthy foods, even

diets.4-6 Thus, short-term use of a reduced-fiber, low-FOD-

after achieving clinical remission. New insights have resulted

MAP dietary approach during a symptomatic IBD flare may

from the investigation of diet and nutrition in the overall care

be helpful, but as patients achieve symptom resolution, we

of patients with Crohn’s disease (CD) and ulcerative colitis

propose that a return to a healthy Mediterranean-style diet

(UC). The aim of this American Gastroenterological Associa-

is in the best long-term interest of patients with IBD.

tion Clinical Practice Update is to provide best practice advice

Adherence to a healthy, balanced Mediterranean diet

statements on the role of diet and nutritional therapies in the

will confer the additional benefit of effectively reducing

treatment of patients with IBD, with a focus on common

intake of ultraprocessed foods, which often contain added

clinical scenarios encountered during IBD care.

sugar, excess salt, and other food additives. High con-

Best Practice Advice 1: Unless there is a contrain-

sumption of ultraprocessed foods has been implicated in the

dication, all patients with IBD should be advised to follow

a Mediterranean diet rich in a variety of fresh fruits and

Abbreviations used in this paper: CD, Crohn’s disease; CDED, Crohn’s

vegetables, monounsaturated fats, complex carbohydrates,

disease exclusion diet; EEN, exclusive enteral nutrition; EN, enteral

nutrition; ESPEN, European Society for Parenteral and Enteral Nutrition;

and lean proteins and low in ultraprocessed foods, added

FODMAP, fermentable oligo-di-and monosaccharide and polyols; GLP-2,

sugar, and salt for their overall health and general well-

glucagon-like peptide-2; IBD, inflammatory bowel disease; IVF, intrave-

being. No diet has consistently been found to decrease

nous fluids; NPO, nil per os (nothing by mouth); PEN, partial enteral

nutrition; PN, parenteral nutrition; PO, per os (by mouth); RD, registered

the rate of flares in adults with IBD. A diet low in red and

dietitian; SBS, short bowel syndrome; UC, ulcerative colitis.

processed meat may reduce ulcerative colitis flares, but

Most current article

has not been found to reduce relapse in Crohn’s disease.

The guidance for consumption of healthy eating pat-

0016-5085/$36.00

terns, such as the Mediterranean diet rich in fruits and

https://doi.org/10.1053/j.gastro.2023.11.303

Table 1.Diets That Have Been Studied in Patients With Inflammatory Bowel Disease

Diet

Description/Rationale

Comments

The Mediterranean diet

Plant-focused diet emphasizing variety of whole grains, fruits, and vegetables.

A recent study (2021)¹ suggested that for adults with mild to moderate CD, the

Main fat source is from fish, olive oil, nuts, and seeds.

Mediterranean diet has similar efficacy to a specific carbohydrate diet.

Lean protein sources are from low-fat dairy, poultry, fish, shellfish, beans,

The Mediterranean diet aligns with a moderate- to high-fiber diet for those in

and/or legumes.

remission.

Higher saturated fat containing meats (ie, red meat) are consumed at much

The Mediterranean diet has demonstrated health benefits separate from IBD,

lower frequency and quantity.

such as reduced cardiovascular disease incidence.

Specific carbohydrate

Nutritionally complete grain-free diet, low in sugar and lactose. Restricts all

Challenging to follow.

diet

hard-to-digest carbohydrates, only eating those that are easy to break down.

There have been limited large-scale studies showing evidence of benefit.

Examples of included foods:

Relatively similar efficacy to Mediterranean diet in DINE-CD (Diet to Induce

Additive free meat and oils (white vinegar, cider, and mustard)

Remission in Crohn’s Disease) trial.

Sugar-free coffee, tea, nut butters, and juice

Low-lactose dairy

Nonstarchy vegetables

Examples of foods not allowed:

Grains and grain products

Candy or foods made with high-fructose corn syrup

High-lactose dairy

Starchy vegetables

Sugars, excluding honey

Hypothesis is that these foods fuel “bad” bacteria in the gut, and thus avoiding

them aids “good” bacterial survival.

Low-FODMAP diet

Elimination rechallenge diet that limits fermentable oligosaccharides,

May be worth trying in patients with IBD who have concomitant IBS-like

disaccharides, monosaccharides, and polyols, which are short-chain

symptoms.

carbohydrates (sugars) that the small intestine absorbs poorly. These are

omitted from the diet for up to 8 wk, then reintroduced 1 at a time.

CDED^a

Whole foods diet designed to limit foods that may adversely affect the

May be worth attempting in patients with mild to moderate CD with short

microbiome or alter intestinal barrier function. Diet is initiated in 3 phases

duration of flares.

and each phase is 6 wk long and includes partial EN (liquid formula either

Allows for some solid foods compared with the 100% liquid nature of EEN;

by mouth or enterically infused).

may improve compliance and be easier to follow.

Phase 1:

Mandatory intake of fish, chicken breast, and eggs

Allows rice, cooled potatoes, tomatoes, onion, garlic, ginger, olive oil, and canola oil

Limited quantities of cucumber, carrots, spinach, lettuce, bananas, apples,

avocados, strawberries, melon, and citrus juices

Phase 2:

Phase 1 foods þ tuna, whole-grain bread, oats, yams, and red peppers

Certain vegetables, beans, peas, turnips, and parsnips are reintroduced after wk 10

Phase 3:

“Maintenance phase”

Phase 1 and 2 foods þ more seafood, eggs, cocoa, coffee, grains, some dairy,

and alcohol if tolerated

^aPlease refer to Figure

March 2024

AGA Clinical Practice Update on Diet and IBD

525

making fibrous, plant-based foods a trigger for obstructive

components of PEN regimens.24,25 The Crohn’s disease

symptoms (Figure 1). Although previous IBD dietary guid-

exclusion diet (CDED) has been studied as a PEN regimen in

ance has suggested avoiding these foods, successful rein-

combination with specific foods.²⁶ The CDED is a whole

troduction of fruits and vegetables can be achieved with

foods diet designed to only exclude or limit foods perceived

careful chewing, as well as cooking and processing of these

to adversely affect the microbiome and/or alter function of

foods to achieve favorable, soft textures that may allow safe

the intestinal barrier. Implemented in 3 phases (phase 1

ingestion of dietary fiber.13,14 Patients readily understand

from week 1-6; phase 2 from week 7-12; and phase 3 from

the difference in texture between a fibrous, unpeeled apple

week 13 forward), it combines PEN with 50% of the calories

(a culprit for obstruction) and the thick, liquid texture of

coming from a nutrition supplement and a small list of

applesauce (easily tolerated) to illustrate this dietary ac-

required foods that are low in fiber, taurine, and saturated

commodation. Patients with IBD in remission who do not

fat. The diet is slowly advanced to incorporate more foods at

have intestinal strictures do not need to limit their fiber

week 7, maintaining 25% of daily calorie intake from PEN in

intake.

phases 2 and 3 (Figure 2). Although initial studies on the

Best Practice Advice 3: Exclusive enteral nutrition

CDED exclusively used the formula Modulen IBD (Nestlé

using liquid nutrition formulations is an effective

Health Science), some providers opt to use alternative oral

therapy for induction of clinical remission and endo-

nutrition supplements.

scopic response in Crohn’s disease, with stronger evi-

In a study by Levine et al comparing the effectiveness of

dence in children than adults. Exclusive enteral

EEN with CDED in children with mild to moderate CD, CDED

nutrition may be considered as a steroid-sparing bridge

was found to be better tolerated than EEN and equally

therapy for patients with Crohn’s disease.

effective for inducing clinical remission by week 6.27-29 In

Best Practice Advice 4: Crohn’s disease exclusion

this same study, the authors found a higher proportion of

diet, a type of partial enteral nutrition therapy, may be

patients sustaining remission after the CDED phase 2 diet

an effective therapy for induction of clinical remission

compared with PEN and usual diet at week 12. A retro-

and endoscopic response in mild to moderate Crohn’s

spective study by Niseteo et al²⁷ had similar results,

disease of relatively short duration.

although they concluded that 1-2 weeks of EEN followed by

Exclusive enteral nutrition (EEN) is a form of intense

the CDED had comparable efficacy to EEN alone for inducing

dietary therapy that demands that the entirety of a person’s

clinical remission of CD in children, and led to better pedi-

caloric intake come from commercially available oral liquid

atric growth trends. In a retrospective analysis, Sigall et al³⁰

meal replacements, excluding all other foods, typically for a

found that CDED may be useful as salvage therapy for pe-

6- to 8-week period.15-17 EEN is usually consumed by

diatric and young adult patients with CD who experience

mouth. EEN is most often initiated in pediatric patients with

loss of response to biologic therapy. Although most of these

CD and is routinely offered as a first-line, steroid-sparing

diets meet key nutritional guidelines, it is prudent to

therapy, achieving clinical remission rates similar to corti-

monitor for nutritional deficiencies.

costeroids (between 60% and 80%).¹⁸ Although EEN is not

Data on the use of EN in the treatment of active UC are

as widely prescribed for adult patients with CD, several

limited. Studies to date suggest that EN is safe and well

studies reported that when tolerated, EEN may be effective

tolerated in patients with UC with severe acute flares and

for inducing clinical and biochemical remission.19-23 It is

can improve prealbumin levels. These preliminary data

important to acknowledge that the lack of definitive adult

suggest a potential clinical benefit in patients with UC who

data is likely related to difficulties in trial recruitment, as

may have difficulty tolerating a regular diet.³¹

well as poor adherence to the EEN regimen itself. The risk of

Best Practice Advice 5: Exclusive enteral nutrition

product fatigue is high with EEN, and adults may find this

may be an effective therapy in malnourished patients

more challenging to ingest day to day, particularly in group

before undergoing elective surgery for Crohn’s dis-

settings where food is being consumed. There is no evidence

ease to optimize nutritional status and reduce post-

to support the use of any one particular EEN product, and

operative complications. Surgery is often required for

standard polymeric formulations are generally well toler-

patients with CD, most commonly for symptomatic intesti-

ated. Prudent selection of products containing nutritional

nal strictures that impair a patient’s ability to tolerate solid

balance and that are calorically individualized to the patient

food. In this setting, liquid nutrition can be attempted to

is key for patient safety. Common products used may be

optimize patients in the preoperative setting.³² Oral EEN

varied amounts of Ensure Plus (Abbott Nutrition), Kate

can be considered in such situations, however, infusion

Farms, among a multitude of polymeric oral supplements, or

through an enteral access device may be indicated in those

traditional EN support products consumed orally, such a

with more severe malnutrition, especially when elemental

Jevity (Abbott Nutrition). The therapeutic mechanism un-

nutrition is being implemented. Recent prospective studies

derlying the success of EEN has not been defined, but easily

in oncologic surgery have confirmed that malnutrition

tolerated texture, low salt content, and a modulatory effect

contributes to excess perioperative morbidity and mortality,

on the microbiome have been hypothesized.

and there are emerging data that correcting malnutrition,

Partial enteral nutrition (PEN) provides an option for

including oral supplementation, can help to reduce this

patients who wish to try therapy with a meal replacement

risk.³³

formula, but are unable to adhere to an EEN regimen. Most

In a prospective study of adult patients with CD and

research has not focused on the specific table food

malnutrition, Costa-Santos et al³⁴ found that preoperative

March 2024

AGA Clinical Practice Update on Diet and IBD

527

oral rehydration solutions) and oral intake whenever

load (eg, soft drinks and sodas), timing of antidiarrheal

possible to decrease the risk of developing long-term

agents with enteral feeding, and medications such as the

complications. Treatment with glucagon-like peptide-2

glucagon-like peptide-2 agonists, which enhance adaptation

agonists can facilitate this transition.

through increase of villous height, crypt depth, and effects

Penetrating and stricturing complications of IBD (ie,

on gastrointestinal motility. Efforts to transition to oral

phlegmon and intra-abdominal abscess) may make

intake and/or continue enteric stimulation should be made

achieving adequate nutrition via the digestive system chal-

whenever possible in the long-term management of SBS.⁴⁵

lenging. Attempts to feed a damaged gut, which has already

Oral rehydration solutions, composed of water, sugar, and

experienced complications, may further worsen clinical

salt are particularly helpful due to the osmolarity having

symptoms and underlying pathology, limiting ability to

affinity for improved intestinal absorption. In patients with

achieve nutritional and caloric goals via the digestive tract

IBD and SBS who are at persistent risk of dehydration,

(oral or enteral nutrition [EN]). Parenteral nutrition (PN)

transition to intravenous solutions with customized elec-

may be warranted in these clinical scenarios to correct

trolytes may be administered as an alternative to PN con-

nutritional deficiency, while allowing the injured gut to rest,

taining calorie support during long-term management.

decreasing microbial contamination of compromised bowel

Ideally, management of patients with IBD with SBS will

and ultimately improving operative outcomes.36,37 When-

benefit from interdisciplinary teams of physicians, midlevel

ever possible, EN (feeding via enteral tube) is the preferred

providers, pharmacists, and registered dietitians (RDs) with

route of nutrition over PN for benefits associated with

expertise in the care of intestinal failure and administration

maintaining gut integrity, function, and for providing vital

of PN.

nutrient source for the microbiota, which has been noted to

Best Practice Advice 9: All patients with IBD war-

reduce infectious complications.38,39 If the gut is accessible

rant regular screening for malnutrition by their pro-

and safe for use, it is the superior route for feeding and it

vider by means of assessing signs and symptoms,

can be used in combination with PN to help achieve nutri-

including unintended weight loss, edema and fluid

tional intake goals.

retention, and fat and muscle mass loss. When

Explicit indications for PN support in the IBD adult pop-

observed, more complete evaluation for malnutrition by

ulation include intestinal failure, being malnourished with

a registered dietitian is indicated. Serum proteins are

clear and definable contraindications to EN, having failed EN

no longer recommended for the identification and

support trials, in patients who lack sufficient bowel function

diagnosis of malnutrition due to their lack of specificity

to maintain or restore nutrition status, in patients who need

for nutritional status and high sensitivity to

to be kept nothing by mouth for at least 7 days before surgery,

inflammation.

and when EN is not feasible or is insufficient to meet total

Best Practice Advice 10: All patients with IBD

nutrient needs for at least 7-10 days.40,41 Examples of when

should be monitored for vitamin D and iron deficiency.

PN may be necessary are high-output intestinal fistulae

Patients with extensive ileal disease or prior ileal sur-

(>500 mL/24 h), high ostomy output (>2000 mL/24 h), and

gery (resection or ileal pouch) should be monitored for

inability to maintain >60% of energy and protein goals via

vitamin B12 deficiency.

either oral nutrition or EN for 7-10 days.

Malnutrition and other nutritional deficits are common,

Historically, patients with IBD who have undergone

underrecognized complications in IBD, especially among

extensive resections comprised a significant subgroup of the

patients with CD and those who have had multiple sur-

population with acquired short bowel syndrome (SBS). SBS

geries. Malnutrition is associated with poor IBD outcomes,

in patients with IBD is an indication for prolonged PN

including increased number of emergency department

support, but this life-saving modality comes with the risk of

visits, increased number and duration of hospitalizations,

central venous catheter complications (ie, central line-

nonelective surgeries, higher mortality, reduced response to

associated bloodstream infections, and thrombotic

medical therapy, and poor quality of life.46-50 European

vascular complications), as well as hepatobiliary complica-

Society for Parenteral and Enteral Nutrition (ESPEN),

tions, such as PN-associated liver disease, hyper-

Academy of Nutrition and Dietetics, and American Society

triglyceridemia, and cholestasis.42,43 The care of patients

for Parenteral and Enteral Nutrition recommend screening

with SBS, including patients with IBD with intestinal failure,

for malnutrition at diagnosis and routinely during long-term

is complex and optimal management was addressed

management in all patients with IBD. RDs can effectively aid

recently in a dedicated American Gastroenterological Asso-

in the diagnosis and treatment of malnutrition in the IBD

ciation Clinical Practice Update.⁴⁴ PN dependance with SBS

population.

is not always indefinite, due to intestinal adaptation, which

Historically, serum proteins, such as albumin, were used

often takes 1-2 years to achieve maximum effect with

to help identify and diagnose malnutrition. However, serum

improved nutrient absorption and slowed gastrointestinal

proteins lack specificity for dietary intake or nutritional

transit. Approximately 50% of adults and 73% of children

status and are highly sensitive to inflammatory activity.

with SBS can wean off of PN support.⁴⁵ Although these ad-

Fluctuation in serum protein levels among patients with IBD

justments are often spontaneous, they may be enhanced

and their variable association with formally diagnosed

through optimized oral dietary intake (separating the bulk

malnutrition have resulted in expert consensus to not use

of liquids from solid foods at mealtime, ie, “dry meals”),

these biomarkers for diagnosing malnutrition.51-54 Hypo-

avoidance of sugar-sweetened beverages with high osmotic

albuminemia is still a useful biomarker in IBD, identifying

528

Hashash et al

Gastroenterology Vol. 166, Iss. 3

patients at higher risk of surgical complications and

homeostasis and improved ability to control chronic

diminished response to anti-tumor necrosis factor therapy.

inflammation.⁶²

The American Society for Parenteral and Enteral Nutri-

All patients with IBD, regardless of age, are at risk for

tion and ESPEN convened an international consensus

anemia. For laboratory screening of iron deficiency anemia, a

statement developing a standardized etiology-based

complete blood count, serum ferritin, transferrin saturation,

approach for identifying malnutrition that focuses on the

and C-reactive protein should be used. For patients in remis-

cause of malnutrition and characterizes severity through a

sion or mild disease, measurements are suggested every 6-12

detailed nutritional history, as well as a practical nutrition-

months. In those with active disease, it is suggested to repeat

focused physical examination.55,56 Malnutrition is charac-

the laboratory screening every 3 months.⁶³ In the presence of

terized by 2 or more of the following: clinically significant

iron deficiency, iron supplementation is advised. Intravenous

weight loss, reduced energy intake, loss of lean mass, loss of

iron is considered more effective, showing a faster response,

subcutaneous fat mass, fluid accumulation, and diminished

and is often better tolerated than oral iron. Oral iron repletion

functional status as demonstrated by formal grip strength

is reasonable in mild anemia, or in those whose disease is

testing. Other notable criteria used for malnutrition

clinically inactive. Dosing is based on baseline hemoglobin and

screening are the Global Leadership Initiative on Malnutri-

body weight.⁶⁴ A detailed review and care pathway addressing

tion criterion and ESPEN criteria. The ESPEN criteria

anemia and iron deficiency in IBD has been published by the

consider body mass index (calculated as kg / m²) <18.5 as a

Crohn’s and Colitis Foundation.⁶⁵

diagnostic criterion for malnutrition.⁵⁷ The Global Leader-

Underdiagnosis of vitamin B12 deficiency in patients

ship Initiative on Malnutrition criteria diagnose malnutri-

with IBD is common because serum blood measurements

tion by the presence of at least 1 of the following

may overestimate body stores.⁶⁶ Prevalence of vitamin B12

phenotypes: clinically significant weight loss, low body mass

deficiency in patients with CD ranges from

5.6% to

index, and reduced muscle mass, and one of the following

38%.66,67 Vitamin B12 homeostasis involves complex ab-

etiologic criteria: reduced food consumption, impaired

sorption of dietary animal protein, requiring adequate sali-

assimilation of nutrients, and inflammation.⁵⁸ The abridged

vary R protein, intrinsic factor from gastric parietal cells,

patient-generated subjective global assessment is a new

and exocrine pancreatic function. The primary uptake site

validated IBD-specific malnutrition screening tool that was

for vitamin B12 is in the terminal ileum. Patients with

published recently.⁵⁹

extensive ileal disease or terminal ileal resection of >30 cm

Malnutrition in patients with IBD most commonly re-

are at an increased risk of vitamin B12 deficiency. Patients

sults from decreased oral intake, increased energy and

with an ileoanal pouch are also at increased risk of vitamin

protein requirements and increased gastrointestinal losses

B12 deficiency due to bacterial overgrowth. Patients with

associated with inflammatory states, malabsorption, disease

active ileal inflammation experience increased metabolism

activity, and SBS, as well as the use of certain medications.

of vitamin B12. Clinical features of vitamin B12 deficiency

In a national sample of inpatients, the relative odds for

include fatigue, anemia, loss of appetite, weight loss, glos-

having malnutrition was 5.57 times higher among patients

sitis, and neuropathy (typically numbness or tingling in

with IBD compared with patients without IBD.⁵⁰ The overall

hands and feet). Neuropathy due to vitamin B12 deficiency

prevalence of malnutrition identified in IBD outpatient

can progress to chronic neuropathic pain and lead to pro-

clinics was 16%, with more than one-half of the malnour-

prioception defects. Yearly screening is warranted in pa-

ished patients having CD (56.8%).47,57

tients at high risk or with clinical features of vitamin B12

Vitamin D, iron, and vitamin B12 are some of the com-

deficiency.⁶⁷ Repletion with 1000 mg of vitamin B12 in-

mon micronutrient deficiencies occurring in patients with

jections (intramuscular or subcutaneous) at 1- to 4-week

IBD. These may arise due to chronic mucosal inflammation,

intervals for life is suggested.⁶⁸ Intramuscular injection re-

excessive dietary restriction, prolonged bowel rest, malab-

sults in more rapid uptake, but subcutaneous injection is

sorption, anatomic changes to length and absorptive ca-

typically more comfortable and readily self-administered.

pacity, and medication-related nutrient interactions. Other

Compared with sublingual vitamin B12 supplementation,

vitamin and mineral deficiencies that are important to

intramuscular or subcutaneous supplementation remains

consider in certain patients with IBD, depending on their

the current preferred route for long-term repletion in pa-

risk factors, include zinc, copper, and fat-soluble vitamin

tients with documented deficiency.

deficiencies, as well as folic acid, especially in patients on

Best Practice Advice 11: All outpatients and in-

methotrexate and sulfasalazine.60,61

Serum values of

patients with complicated IBD warrant co-management

micronutrients may fluctuate in cases of active inflamma-

with a registered dietitian, especially those who have

tion, as many are acute phase reactants (eg, ferritin and

malnutrition, small bowel syndrome, enterocutaneous

copper may increase with inflammation, and zinc, folate, and

fistula, and/or are requiring more complex nutrition

selenium may decrease with inflammation), so it is

therapies (eg, parenteral nutrition, enteral nutrition, or

encouraged to check these levels in patients with quiescent

exclusive enteral nutrition), or those on a Crohn’s dis-

disease and to follow-up after repleting deficiencies. Defi-

ease exclusion diet. We suggest that all newly diagnosed

ciency in vitamin D can lead to loss of bone mineral density

patients with IBD have access to a registered dietitian.

and subsequent metabolic bone disease. Vitamin D defi-

Historically, RDs have played a minor role in the routine

ciency is more often associated with CD. There are emerging

management of patients with IBD due to the lack of

data suggesting a novel role for vitamin D in immune

outpatient access and payor reimbursement. Patients often

AHA/ACC SCIENTIFIC STATEMENT (2024) - page 8