Enteral Nutrition in Severe Acute Pancreatitis

Rudra Prasad Doley
1
, Thakur Deen Yadav
1
, Jai Dev Wig
1
, Rakesh Kochhar
2
, Gurpreet
Singh
1
, Kishore Gurumoorthy Subramanya Bharathy
1
, Ashwini Kudari
1
, Rajesh Gupta
1
,
Vikas Gupta
1
, Kuchhangi Sureshchandra Poornachandra
2
, Usha Dutta
2
, Chetna Vaishnavi
2
Departments of
1
General Surgery and
2
Gastroenterology, Postgraduate Institute of Medical
Education and Research. Chandigarh, India
ABSTRACT
Context There is controversy concerning the merits of enteral and parenteral nutrition in the management of patients with severe
acute pancreatitis. Objective This study was undertaken to evaluate the effect of enteral nutrition versus parenteral nutrition on
serum markers of inflammation and outcome in patients with severe acute pancreatitis. Setting Tertiary care centre in North India.
Design A prospective clinical trial. Methods Fifty consecutive patients with severe acute pancreatitis were randomized in a
prospective trial to receive total enteral nutrition (n=25) or total parenteral nutrition (n=25). Enteral nutrition was delivered distal to
the ligament of Treitz. Serum C-reactive protein, transferrin levels, albumin, surgical intervention, infections, duration of hospital
stay and mortality were compared in the two groups. Results The mean age in the enteral nutrition group was 38.4±13.8 years and in
the total parenteral nutrition group 41.1±11.3 years. The etiological factors were alcohol (n=19), gallstones (n=23), idiopathic (n=7)
and drug-induced (n=1). There was a significant decrease in serum C-reactive protein values in both the enteral nutrition group and
the total parenteral nutrition group at one week and two weeks (P<0.001 for both). Serum albumin rose from a prenutritional value of
2.82±0.51 g/dL to 3.34±0.45 g/dL on day 14 of nutritional support in the enteral nutrition group (P=0.003); in the total parenteral
nutrition group, the level rose from 3.10±0.59 g/dL to 3.21±0.30 g/dL (P=0.638). A significant rise in transferrin value was observed
from day 0 to day 14 in enteral nutrition group (169±30 to 196±36 mg/dL; P<0.001) whereas, in the total parenteral nutrition group,
a less significant difference (191±41 to 201±29 mg/dL; P=0.044) was observed. There was no significant difference in surgical
intervention (56.0% versus 60.0%; P=1.000), infective complications (64.0% versus 60.0%; P=1.000), hospital stay (42 days, 15-108
days, versus 36 days, 20-77 days; median, range; P=0.755), or mortality (20.0% versus 16.0%; P=1.000) in enteral nutrition versus
total parenteral nutrition, respectively. Conclusion Enteral nutrition and total parenteral nutrition are comparable in the management
of severe acute pancreatitis in terms of hospital stay, need for surgical intervention, infections and mortality.
INTRODUCTION
Patients with severe acute pancreatitis suffer from
nutritional impairment during the course of the disease
and nutritional support is mandatory [1, 2, 3, 4]. Total
parenteral nutrition (TPN) and enteral nutrition (EN),
generally delivered beyond the duodenum are the two
options available. While a meta-analysis demonstrated
decreased pancreatic infection rates, need for surgical
intervention, hospital stay and costs in EN patients [5]
and a prospective randomized control study showed a
significantly decreased mortality rate in EN patients
[6], another randomized study showed that total TPN
was more effective in providing increased calories and
proteins in comparison to EN [7]. Yet another recent
meta-analysis of high quality studies has demonstrated
that EN results in clinically relevant and statistically
significant risk reduction of infectious complications,
pancreatic infections and mortality in patients with
predicted severe acute pancreatitis [8]. EN has also
been shown to be beneficial as an adjunct to the
management of severe acute pancreatitis by obviating
the systemic inflammatory response syndrome and in
modifying the course of the disease [9].
Various approaches adopted for nutritional support in
recent clinical trials include TPN, nasojejunal feeding,
nasogastic feeding, and dual enteral and parenteral
nutritional support [1, 10, 11, 12]. Spanier et al. [13]
evaluated nutritional management in a Dutch cohort
(EARL study) and concluded that nutritional
interventions were rapidly undertaken with enteral
feeding via the jejunum as the preferred route. A
critical analysis of trials comparing EN with TPN has
concluded that, although there is evidence to support
EN as the preferred option, both EN and TPN have a
Received September 9th, 2008 - Accepted January 16th, 2009
Key words C-Reactive Protein; Debridement; Enteral Nutrition;
Pancreatitis, Acute Necrotizing; Parenteral Nutrition
Abbreviations CTSI: computed tomography severity index; EN:
enteral nutrition; TPN: total parenteral nutrition
Correspondence Jai Dev Wig
8H/5, Sector-12, PGI Campus, Chandigarh 160 012, India
Phone: +91-172.274.5234; Fax: +91-172.274.4401
E-mail: jdwsjni@hotmail.com
Document URL http://www.joplink.net/prev/200903/10.html

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role [10]. Nutritional supplementation with the addition
of specific agents - immunomodulation and probiotics
is still an unresolved issue [13, 14, 15, 16, 17, 18, 19].
The present study was undertaken to compare the two
forms of nutrition in severe acute pancreatitis as
regards inflammatory markers, serum albumin and
outcome.
METHODS
All patients with severe acute pancreatitis admitted to
Nehru Hospital affiliated with the Postgraduate
Institute of Medical Education and Research,
Chandigarh, India between July 2006 and December
2007 were included in the study. Severe acute
pancreatitis was defined using the Atlanta criteria [20]:
clinical features, hyperamylasemia (three times the
normal upper limit), and radiological evidence of
severe acute pancreatitis (contrast enhanced CT
(CECT) scan evidence of pancreatic necrosis and a
computed tomography severity index (CTSI) equal to,
or greater than, 7). The exclusion criteria were acute or
chronic pancreatitis, patients who had undergone
intervention prior to admission, patients requiring
inotropic support at inclusion, or complications
requiring surgical intervention at the time of inclusion.
Fifty consecutive patients with severe acute
pancreatitis with a CTSI equal to or greater than 7 were
randomized to receive either EN (n=25) or TPN
(n=25). All patients were managed routinely by
gastrointestinal decompression, prophylactic antibiotics
(ciprofloxacin/metronidazole or imipenem/cilastatin),
intravenous fluids and organ system support.
Nutritional support was initiated within 72 hours of
admission and was continued for a minimum of 14
days. The need for further continuation of nutritional
support was decided on the basis of the patients’
clinical status. Image-guided fine needle aspiration or
percutaneous drainage of pancreatic or peripancreatic
collection as a temporizing measure was resorted to in
patients who continued to be toxic.
The characteristics of the study patients are shown in
Table 1. No significant differences were found between
the two groups of patients. Their age ranged from 17-
70 years in EN group and 18-65 years in TPN group.
The etiological factors were alcohol (n=19, 38.0%)
gallstones (n=23, 46.0%), idiopathic (n=7; 14.0%) and
drug-induced (n=1, 2.0%). The mean duration of
presentation was 3.52±0.9 days in the EN group and
3.40±1.29 days in the TPN group.
Data Collection
The following data were collected prospectively from
all patients: i) demographic data including gender, age
and etiology of pancreatitis; ii) clinical data including
number of days of abdominal pain, and paralytic ileus
defined by abdominal distension and absence of bowel
sounds; iii) biochemical data including serum levels of
amylase at hospital admission and thereafter
periodically, serum C-reactive protein (CRP) using the
latex slide agglutination test (Telco Diagnostics,
Anaheim, CA ,U.S.A.) before the initiation of nutrition
and on the 3rd, 5th, 7th and 14th day of nutrition support,
serum albumin and transferrin before the initiation of
nutritional support and repeated on the 7th and 14th day
of nutritional support; iv) radiological data including
pancreatic necrosis and peripancreatic fluid collections
determined by CECT performed before the initiation of
nutritional support and repeated on day 14 to look for
any changes in the CTSI [21]; v) radiological or
surgical intervention; vi) hospital stay and vii)
mortality.
Nutritional Support
Patients were randomized using odd/even numbers to
either enteral nutrition or total parenteral nutrition. The
targeted caloric and protein requirements were 2,500-
2,700 kcal/day, and 120-130 g/day of protein. Feeding
for study purposes was given for 14 days, and the last
evaluation was done on day 14. Jejunal feeding was
started at low flow rates - an initial rate of 20-30 mL/h
until achievement of the full regime of EN.
Delivery of Enteral Nutrition
For placement of an enteral tube, the patients were
shifted to an endoscopic suite and a 16F single lumen
125 cm long red rubber feeding tube was placed over a
400 cm long stainless steel guidewire (Wilson Cook,
Winston, Salem, U.S.A.) beyond the ligament of Treitz
using fluoroscopic control. Seven of 25 patients
required a second attempt at placement of the tube in
the desired position. A test feed with 500 mL of normal
saline was administered over a period of 4-5 hours and
jejunostomy feed was started subsequently. Minor
complications such as diarrhea and distension were
Table 1. Characteristics of study patients.
Enteral nutrition
(No. 25)
Total parenteral
nutrition (No. 25)
P value
Age (years; mean±SD and range)
38.4±13.8
(17-70)
41.1±11.3
(18-65)
0.312 a
Etiology
- Alcohol
- Gallstones
- Idiopathic
- Drug induced
11 (44.0%)
10 (40.0 %)
4 (16.0 %)
0
8 (32.0 %)
13 (52.0 %)
3 (12.0 %)
1 (4.0%)
0.571 b
Duration of pancreatitis at admission (days; mean±SD and range)
3.52±0.92
(1-5)
3.40±1.29
(1-5)
0.373 a
Mann-Whitney U-test
Pearson chi-square test

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managed by altering the infusion rate and adding an
antimotility agent.
Parenteral Nutrition
A 16G central venous catheter was inserted through the
subclavian or internal jugular vein. A chest X-ray was
taken after insertion to check the catheter tip position
and also to check for complications of central venous
line placement. Commercially available parenteral
nutrition formula (PNA: parenteral nutrition admixture;
Claris Lifesciences Ltd., Ahmedabad, India) was
administered. The target caloric and protein
requirements were similar to the enteral group.
Glycemic control and metabolic parameters were
monitored. All patients in the parenteral group could be
weaned to oral diet (those managed conservatively) and
feeding through a jejunostomy catheter placed
intraoperatively (those operated on).
STATISTICS
Statistical data analysis was performed by using the
Statistical Package for Social Sciences (SPSS Inc.,
Chicago, IL, U.S.A.) for Windows version 13.0. A
non-parametric Mann-Whitney U-test was used to
compare the continuous values between groups.
Comparison between pre-nutritional and post-
nutritional variables was carried out using the non-
parametric Wilcoxon signed-rank test. Categorical data
were described as absolute and relative frequencies,
and were compared by the Pearson chi-square or the
Fisher’s exact (2x2 tables) tests. Two-tailed P values of
less than 0.05 were considered statistically significant.
ETHICS
The protocol for the study was approved by Ethical
Committee of our institution and written informed
consent was obtained from all patients. The study
protocol conforms to the ethical guidelines of the
"World Medical Association Declaration of Helsinki -
Ethical Principles for Medical Research Involving
Human Subjects" adopted by the 18th WMA General
Assembly, Helsinki, Finland, June 1964, as revised in
Tokyo 2004.
RESULTS
C-Reative Protein (CRP)
At admission, the CRP level was found to be high in
both groups (Table 2). In the EN group, a decreasing
trend was observed during the course of the nutritional
support. A similar trend was observed in the TPN
group. The decrease in CRP level was statistically
significant in both groups.
Serum Albumin
In the EN group, a significant sequential rise in serum
albumin was observed after admission up to day 14. In
the TPN group, no significant differences were
observed during the course of the nutritional support
(Table 2). However, the two groups did not differ
statistically (Table 2).
Serum Transferrin
In the EN group, a significant rise in transferrin value
was observed during the course of nutritional support
(Table 2). In TPN, the transferrin value also increased
during the course of nutritional support, but the
differences between the two groups were not
statistically different at days 7 and 14 (Table 2).
CTSI
The mean CTSI on admission in the EN group was
8.84±1.07, and it was 9.08±2.08 on the 14th day of
nutritional support. The CTSI increased during the
study period in 8 patients (32.0%) while no change was
observed in 16 patients (64.0%); one patient (4.0%)
showed a reduction in the CTSI. In the TPN group, the
mean index on admission was 8.72±1.14 and was
9.26±1.09 on day 14 of nutritional support. The disease
severity index increased in 7 patients (28.0%) and, in
Table 2. Markers of disease activity at admission and during hospital stay.
Enteral nutrition (No. 25)
Total parenteral nutrition (No. 25)
Mean±SD (range)
vs. day 0 a
Mean±SD (range)
vs. day 0 a
P value
EN vs. TPN b
C-reactive protein
- Day 0
- Day 7
- Day 14
162.3±195.4 (1-822)
31.6±27.9 (2-102)
10.0±11.8 (0-51) c
-
<0.001
<0.001
117.5±118.7 (1-410)
28.6± 44.1 (0-205)
14.0± 24.1 (0-102)d
-
<0.001
<0.001
0.709
0.179
0.692
Serum albumin (g/dL)
- Day 0
- Day 7
- Day 14
2.82±0.51 (2.0-4.0)
3.04±0.49 (2.0-4.0)
3.34±0.45 (2.0-4.0)e
-
0.016
0.003
3.10±0.59 (2.0-4.0)
3.01±0.43 (2.0-4.0)
3.21±0.30 (3.0-4.0) f
-
0.628
0.638
0.058
0.866
0.170
Serum transferrin
- Day 0
- Day 7
- Day 14
169±30 (110-210)
181±40 (100-230)
196±36 (112-240)g
-
0.007
<0.001
191±41 (100-286)
194±28 (138-239)
201±29 (140-243)h
-
<0.001
0.044
0.019
0.466
0.820
CTSI
- Day 0
- Day 14
8.84±1.07 (7-10)
9.08±2.08 (7-10)
-
0.102
8.72±1.14 (7-10)
9.26±1.09 (7-10)
-
0.016
0.684
0.843
CTSI: computed tomography severity index
Wilcoxon signed-rank test
Mann-Whitney U-test
cP<0.001; dP<0.001; eP=0.047; fP=0.018; gP=0.058; hP=0.165 (comparison between day 7 and day 14 a)

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the other 18 (72.0%), the CTSI was unchanged. There
was no significant difference in the CTSI on admission
and on day 14 of nutritional support between the two
groups (Table 2).
Management
Supportive treatment was instituted in all patients. Six
patients (24.0%) in each of the two groups, EN and
TPN, were managed successfully without any
radiological or surgical intervention. Thirteen patients
(52.0%) in the EN group underwent percutaneous
catheter drainage; five of these patients were managed
successfully with percutaneous catheter drainage alone.
In the TPN group, 11 patients (44.0%) underwent
percutaneous catheter drainage and four of them were
managed successfully without surgical intervention.
Therefore, surgical intervention was undertaken in 14
patients (56.0%) in the EN group and 15 patients
(60.0%) in the TPN group. The median time interval to
surgical intervention was 18 days (range: 0-42 days) in
the EN group and 18 days (0-43 days) in the TPN
group (P=0.369). The surgical procedures employed
were pancreatic debridement, closed lesser sac
drainage and placement of a feeding jejunostomy tube
(Table 3).
Morbidity
There was no significant difference in locoregional
complications between the two groups: 13 patients
(52.0%) in the EN group and 10 (40.0%) in the TPN
group had locoregional complications (P=0.571).
Infective Complications
Documented infection was not significantly different
between the two groups (Table 4; P=1.000): 16
(64.0%) patients in the EN group had documented
infection (positive culture of FNA: 5, blood: 5, culture
of operative specimen:11 and culture of drain fluid: 8)
while, in the TPN group, 15 (60.0%) patients had
positive cultures (FNA: 11, blood: 8, operative
specimen: 6,and drain fluid: 5). There was a significant
difference in the organisms found in the two groups
(Table 5). While Escherichia coli was the predominant
organism in the EN group, Staphylococcus aureus,
Enterococci and Candida albicans were more often
found in the TPN group. Statistical significance was
reached only for gram positive organisms (P<0.001).
Mortality
The mortality rate was similar (P=1.000) between the
EN (20.0%) and the TPN (16.0%) groups (Table 4). In
the EN group, all 5 deaths occurred due to sepsis and
multiorgan failure; 4 out of 5 deaths occurred in the
post-operative period. In the TPN group, all 4 deaths
occurred in the post-operative phase: 3 due to sepsis
and multiorgan failure and one due to operative
hemorrhage.
Hospital Stay
There was no significant difference in hospital stay
between the two groups (P=0.755; Table 4). The
duration of hospital stay in the EN group ranged from
15 to 108 days (median 42 days) and, in the TPN
group, it ranged from 20 to 77 days (median 36 days).
Similar behavior was observed for the intensive care
unit (ICU) stay (Table 4).
DISCUSSION
Nutritional support is emerging as a vital component of
the management of severe acute pancreatitis, and
enteral nutrition is reported to be the best nutritional
support in severe acute pancreatitis [2]. EN avoids TPN
complications, maintains intestinal health and may
prevent the progression of multiple organ failure [2].
Table 3. Comparison of surgical procedures in the two groups.
Surgical procedure
Enteral nutrition
(No. 25)
Total parenteral nutrition 
(No. 25)
P value a
Debridement and closed lesser sac lavage and feeding jejunostomy
- After percutaneous catheter drainage
14 (56.0%)
8
15 (60.0%)
7
1.000
Additional procedures
Cholecystectomy
Splenectomy
Ileostomy
Sleeve resection of stomach and gastrostomy
Abscess drainage
7 (28.0%)
3
2
1
1
0
6 (24.0%)
b
b
0
0
1
1.000
Re-exploration
1 (4.0%)
1 (4.0%)
1.000
Fisher’s exact test
One patient had two procedures: cholecystectomy and splenectomy
Table 4. Outcome in the two groups.
Enteral nutrition (No. 25)
Total parenteral nutrition (No. 25)
P value
Infection
16 (64.0%)
15 (60.0%)
1.000 a
ICU stay (days; median and range)
10 (0-44)
15 (0-60)
0.625 b
Hospital stay (days; median and range)
42 (15-108)
36 (20-77)
0.755 b
Mortality
5 (20.0%)
4 (16.0%)
1.000 a
ICU: intensive care unit
Fisher’s exact test
Mann-Whitney U-test

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This prospective randomized study focused on the
effects of EN delivered beyond the ligament of Treitz
via an endoscopically-placed nasojejunal feeding tube
and compared it with TPN. It has been suggested that
EN ameliorates the inflammatory response better than
TPN in severe acute pancreatitis [22, 23]. Both forms
of nutritional support helped in significantly reducing
serum CRP levels during the period of nutritional
support in our study. In patients with infective
complications, the serum CRP level was significantly
high until day 5 in the EN group and until day 7 in the
TPN group as compared to patients without infective
complications (data not shown). Other studies have
also not shown any significant reduction in CRP levels
after 7 days in the enteral feeding group; Loule et al.
[22] reported that CRP levels were reduced to 50% of
the enrolment levels a average of 5 days faster for EN
than TPN, and Zhao et al. [23] found a reduction of
CRP on day 4 in the EN group and on day 7 in the TPN
group.
Powell et al. [24] reported that early EN did not
ameliorate the inflammatory response in patients with
severe acute pancreatitis. In their study, the
introduction of EN did not affect the serum
concentrations of interleukin-6 (IL-6), soluble tumor
necrosis factor receptor I (STNFRI) and CRP over the
first 4 days of the study. Pearce et al. [16] have shown
that, after 3 days of feeding, 13% of patients had
reduced their CRP by 40 mg/L or more in the study
group. In the control group, 3.8% of patients had
reduced their CRP by this amount. Serum transferrin
levels rose significantly in both the EN and the TPN
groups in our study, corresponding to the changes in
serum CRP. The improvement was more marked,
however, in EN group (Table 2).
In our study, the serum albumin level increased
gradually during the nutritional support in both groups.
The increase in albumin levels was found from the
beginning of nutritional support in the enteral group. In
the TPN group, a significant increase was observed
only between day 7 and day 14 days of nutritional
support. Loule et al. [22] observed that both EN and
TPN were equally effective in improving serum
albumin level. Zhao et al. [23] showed a significant
increase of body weight and pre-albumin levels in the
EN group while serum albumin levels were not
increased. In another study regarding EN, serum
albumin concentration increased from 3.0 to 3.8 g/dL
(P<0.001) [25].
There are limited studies on the effect of nutritional
support on the CTSI. No significant difference has
been reported on CECT findings in the studies reported
[22, 26, 27]. We looked at the change in the CTSI at 14
days after admission, and a significant increase of the
CTSI score was seen in the TPN group. However, there
was no significant difference in the CTSI score
between the two groups both at admission and after
nutritional support. Makola et al. [25] have reported a
decrease in the CTSI from 4 to 2 in their patients
following enteral nutrition. Our patients had a much
higher CTSI at admission than those reported by
Makola et al. [25] denoting a more severe disease state
which still evolved in the following14 days.
The type of nutrition has also been shown to influence
infectious complications. Petrov et al. [6] reported
significantly lower infections in the EN group as
compared to the TPN group. We found similar rates of
infection in the two groups (Table 4). However, there
was a striking difference in the type of organisms
found in the two groups (Table 5). Patients given TPN
were more often infected by gram-positive organisms
and fungi as compared to those given EN who were
more often infected by a gram-negative organism. This
observation has an important bearing on the outcome
of severe acute pancreatitis as fungal infection carries a
higher risk of mortality. Though proper aseptic
precautions were maintained, the occurrence of
infections with gram positive organisms such as
Staphylococci in the TPN group suggests that it could
be due to the invasion of central line catchers with
cutaneous commensals.
In our study, no significant difference was found in the
rate of surgical intervention in either group. Modena et
al. [26] reported a significantly lower rate of surgical
intervention in the EN group. In their series, 38 out of
43 patients (88.4%) in the TPN group required surgical
intervention versus 11 patients out of 44 (25.0%) in the
EN group (P<0.01). Petrov et al. [6] also reported a
lower surgical intervention rate in the EN group as
compared to the TPN group. Our observations are
different, perhaps due to a more severe disease state in
our patients. There was no significant difference in
hospital stay in the two groups; the median duration of
the hospital stay was 42 days for the EN group, and 36
Table 5. Organisms found in the two groups.
Organism
Enteral nutrition (No. 25)
Total parenteral nutrition (No. 25)
P value a
Gram negative:
- Escherichia coli
- Acinetobacter
- Proteus
- Klebsiella
- Pseudomonas
18 (72.0%)
12
5
0
1
0
14 (56.0%)
5
4
2
2
1
0.377
Gram positive:
- Staphylococcus aureus
- Enterococchi
2 (8.0%)
2
0
15 (60.0%)
11
4
<0.001
Fungi:
- Candida albicans
2 (8.0%)
2
7 (28.0%)
7
0.138
Fisher’s exact test

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days for the TPN group. Some studies have shown a
reduced hospital stay in the EN group [28, 29] and
several studies have reported a reduced mortality rate
in the EN group. Modena et al. [26] and Petrov et al.
[6] have reported significantly lower mortality rates in
the EN group as compared to the TPN group. In our
study, no significant difference was observed between
the EN (20.0%) and the TPN (16.0%) groups.
In conclusion, our prospective study has shown that
TPN and EN were equally effective in ameliorating the
inflammatory response and improving the nutritional
status of the patients. Mortality, hospital stay and ICU
stay were also similar in the two groups. The two forms
of nutrition differed, however, in terms of infective
organisms. The use of TPN was more often associated
with infection with gram positive and fungal organisms
whereas the use of EN was associated with gram
negative organisms.
Conflict of interest The authors have no potential conflicts of
interest
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