N u t r i t i o n a l Ma n a g e m e n t o f

A c u t e Pa n c re a t i t i s
Kavin A. Kanthasamy, MDa,*, Venkata S. Akshintala, MDb, Vikesh K. Singh, MD, MScc

KEYWORDS
 Acute pancreatitis  Nutrition  Enteral nutrition

KEY POINTS
 Acute pancreatitis (AP) remains among the most common gastrointestinal disorders
requiring hospital admission.
 EN further preserves gut function by reducing gut dysmotility and ileus promoted by
pancreatic and systemic inflammation.
 However, poor tolerance of EN and the spectrum of disease severity in patients with AP
present unique challenges for clinicians in determining the appropriate type, timing, route,
and composition of nutritional support, which results in significant variation in manage-
ment across centers.

INTRODUCTION

Acute pancreatitis (AP) remains among the most common gastrointestinal disorders
requiring hospital admission. The burden and cost of AP on the health care system
continues to rise accounting for nearly 280,000 hospitalizations and more than $2.6
billion dollars spent annually in the United States.1 The management of AP is largely
supportive and focuses on intravenous fluid therapy, analgesics, and nutritional sup-
port. Enteral nutrition (EN) is one of the few interventions that has been shown to
reduce mortality in AP2 and plays a key role in limiting disease progression and accel-
erating patient recovery.
The pathogenesis of AP across all etiologies involves a complex cascade of intra-
acinar pancreatic zymogen activation, most notably trypsinogen, resulting in acinar
injury and upregulation of proinflammatory mediators and cytokines that contribute
to a profound local and systemic inflammatory response syndrome (SIRS).2 Nutritional
support plays a key role in mitigating the sequelae of the SIRS response with specific
attention to hypoperfusion of the gut barrier mediated by inflammatory and microcir-
culatory damage.3 EN is thought to promote the integrity of the damaged gut barrier by

a
Division of Gastroenterology, Johns Hopkins Medical Institutions, 1800 Orleans Street, Bal-
timore, MD 21287, USA; b 1800 Orleans Street, Sheikh Zayed Tower, Baltimore, MD 21287, USA;
c
1830 East Monument Street, Room 428, Baltimore, MD 21205, USA
* Corresponding author.
E-mail address: [email protected]

Gastroenterol Clin N Am 50 (2021) 141–150

https://doi.org/10.1016/j.gtc.2020.10.014 gastro.theclinics.com
0889-8553/21/ª 2020 Elsevier Inc. All rights reserved.
142 Kanthasamy et al

preventing luminal mucosal atrophy, hence reducing gut permeability and the resulting
translocation of gut microbiota that potentiates AP-associated SIRS, multiorgan fail-
ure, and infection (Fig. 1).4,5 EN further preserves gut function by reducing gut dysmo-
tility and ileus promoted by pancreatic and systemic inflammation. Ileus has been
associated with infected pancreatic necrosis in patients with necrotizing AP, likely a
reflection of the paradigm of bacterial translocation.6 The inflammatory response
also induces a highly catabolic state that increases metabolic demand causing a
negative nitrogen balance of up to 20 to 40 g per day that promotes malnutrition.7,8
For these reasons, optimizing nutritional support and maintaining gut function is
instrumental in the recovery of patients with AP. However, poor tolerance of EN and
the spectrum of disease severity in patients with AP present unique challenges for cli-
nicians in determining the appropriate type, timing, route, and composition of nutri-
tional support, which results in significant variation in management across centers.9
This review summarizes the current evidence with regard to these questions and pro-
vides recommendations in line with current consensus opinions to guide the clinical
management of AP from the perspective of nutritional support.

ORAL NUTRITION AND TIMING

Historically, the initial management of AP prioritized bowel rest with nil per os (NPO)
status with the rationale that avoiding EN would minimize pancreatic stimulation
and any exacerbation of ongoing inflammation. In normal patients, oral/duodenal
feeding leads to greater stimulation of pancreatic exocrine function compared with
fasting and intravenous nutrition as measured by rates of duodenal trypsin secretion
(Table 1).10,11 Middistal jejunal feeding, however, does not seem to stimulate
pancreas exocrine secretion.9 AP has been shown to diminish pancreatic exocrine
function and the effect seems proportional to morphologic disease severity with the
lowest rates of trypsin secretion seen in necrotizing pancreatitis (see Table 1).12
This suggests that pancreatic exocrine function may be “stunned” in AP and EN,
regardless of the route, especially in necrotizing AP, may not produce appreciable
pancreatic stimulation to contribute to worsening disease severity. Furthermore, EN
has been shown to promote gut integrity and function, introducing the concept of

Fig. 1. Pathophysiology of acute pancreatitis and mitigation of associated gut barrier

dysfunction by enteral nutrition. IL, interleukin; TNF, tumor necrosis factor.
 Nutritional Management of Acute Pancreatitis 143

Table 1
Pancreatic enzyme secretory response to various forms of diet

Mode of Feeding Trypsin (u/h)

Normal patients
Fasting (n 5 7) 134 (22)
Intravenous (n 5 5) 171 (33)
Duodenal total (n 5 13) 408 (51)
Polymeric (n 5 6) 471 (73)
Elemental (n 5 7) 335 (65)
Middistal jejunal (n 5 11) 119 (16)

Disease Severity Trypsin (u/h)

AP
Control, no AP (n 5 8) 514  86
Mild/moderate (n 5 8) 214  83
Necrotizing (n 5 4) 32  7

Duodenal trypsin secretion rates in normal patients given various modes of feeding and in patients
with AP given duodenal feeding. Values are listed as group means with standard error.
Data from Kaushik N, Pietraszewski M, Holst JJ, O’keefe SJ. Enteral feeding without pancreatic
stimulation. Pancreas. 2005;31(4):353-9; and O’keefe SJ, Lee RB, Anderson FP, et al. Physiological
effects of enteral and parenteral feeding on pancreaticobiliary secretion in humans. Am J Physiol
Gastrointest Liver Physiol. 2003;284(1):G27-36.

“gut rousing, but not resting.”13,14 In line with this, contemporary evidence supports
early enteral feeding, ideally per os in AP.
A recent systematic review of 11 randomized control trials (RCTs) by Vege and col-
leagues15 compared the role of early feeding (within 48 hours of admission) with
delayed feeding across all severities of AP and found no difference in outcomes
including mortality, rates of multiorgan failure, and complications related to pancreatic
necrosis. Prior systematic reviews have also shown decreased length of stay (LOS)16
and potentially lower infectious complications17,18 with early feeding within 48 hours of
admission. The American Gastroenterological Association (AGA) guidelines for AP
currently strongly recommend early (within 24 hours) oral feeding as tolerated rather
than keeping patients NPO based on this moderate quality body of evidence.19 Mul-
tiple RCTs suggest initiation of oral feeding upfront with a soft low-fat, low-residue diet
because it provides more calories without worsening of symptoms or difference in
LOS when compared with an initial diet of clear liquids.20–22
It is important to acknowledge that oral refeeding is sometimes not feasible in pa-
tients with significant symptoms, gastrointestinal dysmotility, and in severe AP
(SAP)/necrotizing disease. For these patients, timely initiation of EN via a nasogastric
tube (NGT) or nasojejunal tube (NJT) becomes appropriate. However, the administra-
tion of prompt EN via NGT/NJT as a substitute for oral intake in patients with predicted
SAP is not associated with improved outcomes. The PYTHON trial, a multicenter RCT
from the Netherlands, that randomized patients with predicted SAP (defined as Acute
Physiology and Chronic Health Evaluation II score of 8, an Imrie or modified Glasgow
score of 3, or a serum C-reactive protein level of >150 mg/L) to either early EN via
NGT within 24 hours of admission or to “on-demand” oral feeding within 72 hours,
found no differences in the composite end points of major infection and death or in
secondary end points of rates of pancreatic necrosis or need for intensive care unit
level care.23 Of note nearly 70% of patients in the on-demand group were able to
144 Kanthasamy et al

tolerate oral feeding in the early stages of disease and had shorter time to tolerance of
full oral feeding (6 days for oral group vs 9 days for EN group). Additional studies have
demonstrated no difference in inflammatory profiles/cytokine production in oral versus
EN in SAP.24 Although more research is needed to clarify the optimal timing and
administration of EN in severe and acute necrotizing pancreatitis, early oral feeding
in this subgroup may be trialed cautiously and directed by patient symptoms.

TYPE OF NUTRITION (ENTERAL NUTRITION VS PARENTERAL NUTRITION)

The previously held dogma of gut and pancreatic rest in AP established parenteral
nutrition (PN) as the primary means of providing nutrition while patients were kept
NPO. Current evidence, however, has clearly shown worse outcomes with PN rela-
tive to EN. In a technical review of 12 RCTs that compared EN with PN across all se-
verities of pancreatitis, there was more than a two-fold reduction in the rate of
multiorgan failure (odds ratio, 0.41; 95% confidence interval, 0.27–063) and nearly
a four-fold reduction in infected peripancreatic necrosis (odds ratio, 0.28; 95% con-
fidence interval, 0.15–0.51) with the use of EN.15 Other meta-analyses have also
shown increased cost, infectious complications, and LOS with the use of PN.25,26
These findings were similarly shown in a Cochrane review by Al-Omran and col-
leagues of eight RCTs that also demonstrated increased mortality in the subset of
patients with SAP receiving PN.27 These findings are likely reflective of known com-
plications inherent to PN, such as to catheter-related bloodstream infections and
sepsis, metabolic derangements,11 and compromise of gut barrier function and
microbiota dysbiosis that has been demonstrated with the withdrawal of EN in crit-
ically ill patients.28,29
In patients unable to tolerate oral feeding within the first 48 to 72 hours because of
symptoms, ileus, or SAP, EN via NGT or NJT should be prioritized over PN in line with
the current strong recommendation from the AGA that was based on moderate-quality
evidence.30 Given the relative harm associated with PN, it should be reserved only for
patients unable to tolerate EN over a prolonged period, when an NGT/NJT cannot be
placed, or when minimal caloric needs cannot be met with EN alone.

ROUTE OF ENTERAL NUTRITION (NASOGASTRIC VS NASOJEJUNAL)

Despite clear evidence supporting the use of EN in patients intolerant of oral feeding,
there is less compelling evidence for a preferred route: NGT versus NJT. A meta-
analysis of three RCTs that compared NGT with NJT feeding in SAP demonstrated
no difference in mortality, infectious complications, or LOS.31 The distal delivery of
EN via NJT offers a theoretic reduction in aspiration risk and middistal jejunal nutrition
has been shown to minimize pancreatic stimulation. However, RCTs and meta-
analyses have shown no difference in tracheal aspiration,30 exacerbation of pain, or
energy balance between the two routes.32 These studies had several limitations
including large heterogeneity, high risk of bias because of a lack of blinding, small
sample sizes, and poorly specified outcomes. A large multicenter trial comparing
NGT with NJT feeding in AP was unfortunately terminated because of lack of adequate
patient recruitment (ClinicalTrials.gov NCT00580749). The lack of clear evidence sug-
gesting a superior route of EN in SAP may reflect stunning of pancreatic exocrine func-
tion observed in necrotizing disease.
Although available evidence is not robust, NGT represents a more pragmatic option
for EN in AP given the relative ease of bedside placement compared with endoscopic
placement of NJT. There are new bedside transnasal systems that have been devel-
oped for the placement of NGT and NJT. Additional research is required to more
 Nutritional Management of Acute Pancreatitis 145

definitively establish the optimal and safest route of EN in SAP; however, results of the
PYTHON trial demonstrating equal tolerance of oral feeding compared with tube
feeding in SAP may make the comparison less relevant for clinical management.

COMPOSITION OF ENTERAL NUTRITION AND IMMUNONUTRITION

There is a wide range of EN formulations with varying purported benefits in AP and, for
simplicity, is divided into three categories: (1) oligomeric feeds, (2) polymeric feeds,
and (3) “immunonutrition.” Oligomeric, also known as semielemental, formulations
contain small peptides, medium-chain fatty acids, and simple polysaccharides that
do not require digestion by pancreatic enzymes and theoretically offer greater pancre-
atic rest than more complex polymeric formulations that contain full proteins, complex
lipids, and carbohydrates.33,34 Two meta-analyses, however, comparing oligomeric
with polymeric formulations found no difference in terms of feeding intolerance, mor-
tality, or LOS between the two formulations.35 There is no apparent clinical advantage
to the use of oligomeric formulations and more inexpensive polymeric formulations
should be readily used.
Immunonutrition broadly refers to specialized formulations containing immunomod-
ulatory supplements that are thought to offer benefit by modifying the immune
response associated with AP. The most well studied of these include formulations
supplemented with one of either glutamine, arginine, omega-3 fatty acids, nucleo-
tides, and fiber enrichment. Trials in other clinical settings involving critically ill patients
given immunonutrition-supplemented EN, specifically with glutamine and arginine,
have described trends toward lower infectious complications and mortality compared
with standard EN.36–38 The benefit of immunonutrition-supplemented EN in AP is less
established and based on low-quality studies. A Cochrane systematic review by Poro-
pat and colleagues39 of 15 trials investigating EN formulations specifically containing
immunonutrition components given to patients with AP found no difference in all-
cause mortality or occurrence of SIRS when compared with other EN formulations.
Nearly all the trials in this review were noted to be of low quality with a high risk for
bias. A separate meta-analysis by Petrov and colleagues40 similarly did not demon-
strate a clinical benefit with immunonutrition formulations in regard to LOS or infec-
tious complications.
There are trials, largely from China, showing clinical benefit of PN supplemented
with glutamine or glutamine administered intravenously in SAP with regards to lower
infectious complications, LOS, and resolution of inflammatory markers.41–44 Gluta-
mine is postulated to exert an immunomodulatory effect via increasing lymphocyte
mitogenic function, whereas decreasing production of proinflammatory cytokines,
such as interleukin-6 and tumor necrosis factor-a and antioxidant properties. Gluta-
mine also supports the growth of other rapidly dividing cells, such as enterocytes.45
These benefits have not been demonstrated in trials with glutamine-supplemented
EN,43,46 currently limiting the clinical relevance of glutamine in AP until further investi-
gation with high-quality trials can be performed.
Patients with AP are known to have gut dysbiosis or unfavorable imbalance of gut
microbiota that may contribute to associated inflammation.3,47 The use of probiotics,
substances containing live microorganisms of healthy gut flora, however, has been
shown to be detrimental in AP. The PROPATRIA trial, a multicenter, double-blind, pla-
cebo-controlled RCT of nearly 300 patients with predicted SAP conducted in the
Netherlands aimed to reduce infectious complications in patients with SAP through
the use of enteral probiotic preparations. The study compared the use a multispecies
mixture of two different Bifidobacterium species, three different Lactobacillus species,
146 Kanthasamy et al

and one Lactococcus species with placebo. Findings from the trial demonstrated no
significant difference in the primary end point of infectious complications and a two- to
three-fold increase in mortality in patients who received probiotics.48 Until more
studies can establish an acceptable safety margin and consistent dosing for probiotic
administration, their use should be avoided in AP.
The benefit of immunonutrition in AP is currently unclear and, as recommended by
the AGA, warrants further investigation with high-quality RCTs to support routine use.
Current evidence is lacking in supporting the use of immunonutrition-supplemented
EN but there may be some benefit of glutamine-supplemented PN in patients with
SAP requiring PN. A Cochrane systematic review and network meta-analysis by
DiMartino and colleagues49 is ongoing to further clarify the benefit of immunonutrition
supplementation in EN and PN in AP.

SUMMARY AND RECOMMENDATIONS

In addition to supportive care, nutritional support is a cornerstone of the management

of AP across all disease severities. EN serves to preserve the gut barrier as a means to
mitigate immune dysregulation and systemic inflammation inherent to the clinical syn-
drome of AP. Based on the current body of evidence, oral feeding trials should be initi-
ated generally within 24 hours with a soft, low-residue diet as tolerated rather than
routinely keeping patients NPO. Polymeric EN should be given via tube feeding for pa-
tients unable to tolerate an oral feeding challenge within 48 to 72 hours. NGT may be
the preferred route of feeding in patients without gastric outlet obstruction, ileus, or of
high aspiration risk because of its relative convenience and lack of evidence support-
ing the superiority of NJT (Fig. 2). It is important to actively reassess patients reported
symptoms to attempt oral feeding trials as feasible. PN should be avoided because of
worse clinical outcomes relative to EN and is reserved only for select situations where
EN cannot be administered. Immunonutrition formulations cannot be routinely

Fig. 2. Flow diagram on the suggested nutritional management of patients with moderate
to severe acute pancreatitis (pancreatic necrosis). GOO, gastric outlet obstruction; NG, naso-
gastric; NJ, nasojejunal; TEN, total enteral nutrition; TPN, total parenteral nutrition.
 Nutritional Management of Acute Pancreatitis 147

recommended based on current evidence and additional investigation is required to

clarify its benefit in AP. Probiotic use should be avoid in AP.

CLINICS CARE POINTS

 Oral and enteral nutrition (EN) significantly reduces the risk of mortality, infection, and
organ failure in patients with acute pancreatitis and should be prioritized along with fluid
therapy and analgesia.
 Oral feeding using a soft low-fat and low-residue diet should be attempted within 24 hours
of presentation as tolerated by symptoms rather than keeping patients nil per os (NPO). Early
oral feeding is safe and has been shown to decrease hospital length of stay.
 Patients unable to tolerate oral feeding trials over 48 to 72 hours should receive EN through a
feeding tube. There is no difference between nasogastric or nasojejunal tubes and the choice
of which to use is left to the discretion of the clinician and available resources.
 Parenteral nutrition should be avoided in acute pancreatitis because of increased rates of
infection and mortality relative to EN. Its use is reserved for only select circumstances
where EN is not tolerated.
 The benefit of “immunonutrition” and other nutritional supplements in acute pancreatitis
requires further investigation. Probiotic use should be avoided.

DISCLOSURE

All included authors disclose no commercial or financial conflicts of interest.

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