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Gang
Zhao, Chun-You Wang, Jiong-Xin Xiong, Pancreatic Surgery Center,
Union Hospital, Tongji Medical College, Huazhong University of
Science and Technology, Wuhan 430022, Hubei Province, China
Fang Wang, Department of Pharmacology, Tongji Medical
College, Huazhong University of Science and Technology, Wuhan
430030, Hubei Province, China
Correspondence to: Dr. Gang Zhao, Pancreatic Surgery Center,
Union Hospital, Tongji Medical College, Huazhong University of
Science and Technology, Wuhan 430022, Hubei Province, China. zhaogang1427@yahoo.com.cn
Telephone: +86-27-85726273
Received: 2003-03-20
Accepted: 2003-04-22
Abstract
AIM: To investigate the effect of nutritional support therapy on
severe acute pancreatitis (SAP).
METHODS:
A total of 96 patients with severe acute pancreatitis were divided
randomly into control and treatment groups. The former group
received total parenteral nutrition (TPN) via central venous
infusion, while parenteral nutrition (PN) and enteral nutrition (EN)
therapies were applied in different phases for the latter group. The
nutrition status, acute phase responses, pancreas lesions, enteric
mucosa penetrability and immune functions were monitored.
RESULTS:
Body weight and prealbumin concentration were increased in treatment
group, compared to those in the control group, but albumin
concentration did not change significantly. Acute physiology and
chronic health evaluation II (APACHE II) scores decreased after 7 d
of treatment, whereas the scores of the control group decreased on
the 11th day. Concentrations of tumor necrosis factor-a
(TNF-a),
interleukine-6 (IL-6) and serum C reactive protein (CRP) dropped
earlier in the treatment group (on the 4th day) than that
in the control group (on the 7th day). No difference was
observed in pancreatic lesions between the control and treatment
groups. Concentration of endotoxin and lactulose/manicol (L:M) ratio
of urine did not change in treatment group, but those in the control
group were elevated markedly. Compared with the treatment group,
CD4:CD8 T cells ratio and immunoglobulin G (IgG) concentration in
the control group decreased significantly.
CONCLUSION:
Compared to TPN, the combined therapy of EN and PN could improve the
nutrition status and moderate the acute phase response obviously.
Moreover, the integrity of enteric mucosa and immune function were
protected more effectively in treatment group than in the control
one. On the other hand, EN did not simulate the excretion of
pancreas and avoid exaggerating the inflammation of pancreas. Thus,
appropriate application of PN and EN appears to be more effective
for patients with SAP.
Zhao
G, Wang CY, Wang F, Xiong JX. Clinical study on nutrition support in
patients with severe acute pancreatitis. World J Gastroenterol 2003; 9(9): 2105-2108
http://www.wjgnet.com/1007-9327/9/2105.asp
INTRODUCTION
Severe acute pancreatitis (SAP) is characterized by a diffuse
inflammatory process of the pancreas with variable involvement of
adjacent tissues and dysfunction of remote organs[1]. The
metabolic alterations of SAP are involved in a classical stress
state, as proposed for sepsis, including hyperdynamic changes,
hypermetabolism and hypercatabolism. Thus, artificial nutritional
support should be a suitable treatment[2-4]. The clinical
nutritional management of pancreatitis has changed from total
parenteral nutrition (TPN) to enteral nutrition (EN). However, it
remains to be clarified whether EN is the best approach or not[5-8].
The purpose of this observation was to evaluate different nutrition
therapies for SAP.
MATERIALS
AND METHODS
Patients
A total of 96 patients with SAP admitted to the Pancreatic
Surgery Center of Union Hospital (Wuhan, China) between February
2000 and October 2002 were recruited to the randomized study. The
severity of pancreatitis was defined according to the Atlanta
classification system for acute pancreatitis. Criteria for this
observation were the acute physiology and chronic health evaluation
II (APACH II) score higher than 8, and no indication for operation
temporarily[9, 10]. These patients consisted of 58 males
and 38 females with a mean age of 47.8 years (range 24-68 years).
After 48 hours of common management including active liquid
resuscitation and organ function protection[11,12], the
patients were divided randomly into control and treatment groups. No
significant differences of male:female ratio (15.6:16.7) and average
age (48.2 and 46.7) were found between the two groups.
Study
protocol
The 41 patients in control group were commenced on TPN via
central venous infusion. In the treatment group, PN and EN were
carried out by three stages for 55 patients. At first, the patients
of treatment group only received glutamine-supplemented PN. When the
paralysis was relieved, EN and PN were applied at the same time. EN
was administrated via a nasojejunal feeding tube under endoscopy or
X-ray. Following the study period, the volume and speed of enteral
feeding were adjusted depending on the individual tolerance.
Deficiency of energy was compensated through glutamine-supplemented
PN. At last, the enteric feeding reached approximately 2 000 ml in
5-7 d, and PN was ceased.
Nutrition
formulas
Conventional TPN was based on an amino acid solution
providing 0.25 g nitrogen/(kg·d) with lipid emulsion and glucose.
Half of the non-protein calories were provided by lipid. The total
calorie was 30 kcal/(kg·d) and the calorie to nitrogen ratio was
120:1 in each patient. Electrolytes, trace elements and vitamins
were added to maintain requirements [13].
PN in treatment group was based on the same elements as TPN
but with supplement of 0.22 g glutamine/kg. EN formula was
Peptide-2000 (Nutricia, Holland) semi-elementary diet (2.9 g
nitrogen and 500 kcal non-protein calorie/500 ml), with supplement
of glutamine tablets to increase the intake of glutamine[14,15].
Experimental
protocols
Body weight, albumin and prealbumin concentrations were
determined to evaluate the nutrition status once of a week. APACH II
scores, serum C reactive protein (CRP), tumor necrosis factor-a
(TNF-a)
and interleukine-6 (IL-6) were quantified every three days to assess
the acute phase response. Pancreatic and peripancreatic necrosis
were detected by contrast-enhanced CT scan once a week. These
results of CT scan were scored with a modified Balthazar scoring
system. Permeability of gastrointestinal mucosa was evaluated by
concentration of endotoxin and lactulose/manicol (L:M) ratio of
urine. CD4:CD8 ratio of T cell and concentration of immunoglobulin G
(IgG) were quantified to assess immunological function.
Statistical
analysis
All data were expressed as the mean ± standard deviation.
Student's t test was used to analyze the difference. A value of P<0.05
was considered statistically significant.
RESULTS
Nutrition status
Compared to the control group, body weight and plasma
prealbumin concentration were increased in the treatment group after
two weeks of treatment (P<0.05), whereas plasma albumin
concentration did not change (Table 1).
Acute phase responses
APACH II scores decreased earlier in the treatment group (on the
4th day) than those in the control group (on the 7th
day). Moreover, the concentration of serum CRP, TNF-a
and IL-6 in treatment group decreased earlier too (Table 2).
Pancreas
lesions
The concentrations of serum and urine amylase in both groups
decreased on the 7th day, and there were no significant
differences between these two groups. Similar changes were observed
in the CT scores (Table 3).
Enteric
mucosal permeability
Few endotoxins were detected in the treatment group on the 7th
day, and the urine L:M ratio remained unchanged. Endotoxin
concentration and urine L:M ratio in control group elevated
gradually and were much higher than those in the treatment one (P<0.05)
(Table 4).
Immune
function
CD4:CD8 T cell ratio and serum IgG concentration did not
change in the treatment group. In control group, CD4:CD8 T cell
ratio and serum IgG concentration decreased continuously and were
markedly lower than those in the treatment group (P<0.05)
(Table 5).
Table
1 Changes
of body weight, plasma albumin and prealbumin concentrations in two
groups
|
1
d |
7
d |
14
d |
21 d |
|
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
| Weight
(kg) |
66.5±13.4 |
65.7±13.1 |
56.9±13.1 |
55.4±13.5 |
55.7±12.9 |
60.4±13.4a |
58.81±4.2 |
63.2±13.2a |
| Albumin
(g/L) |
38.7±5.2 |
38.8±3.9 |
33.4±4.1 |
33.8±3.7 |
35.2±4.3 |
36.5±2.9 |
37.3±4.5 |
38.7±5.1 |
| Prealbumin(g/L) |
12.6±3.2 |
12.7±5.2 |
8.4±2.9 |
11.1±2.2a |
9.6±4.1 |
12.5±5.1a |
11.9±6.1 |
12.7±5.9 |
aP<0.05
vs control.
Table
2 Changes
of APACHE II scores and concentration of TNF-a,
IL-6 and CRP in two groups
|
1
d |
4
d |
7
d |
11
d |
15
d |
|
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
| APACH
II |
8.2±0.7 |
8.3±0.6 |
8.4±0.9 |
7.9±0.6a |
7.1±0.8 |
5.7±0.7a |
5.2±0.7 |
3.7±0.8a |
1.6±0.4 |
1.5±0.5 |
| TNF-a(pg/ml) |
63.5±15.2 |
68.4±13.5 |
55.6±16.3 |
47.4±11.6a |
43.9±9.7 |
34.2±7.6a |
34.6±7.5 |
14.2±3.2a |
16.5±9.6 |
15.4±5.3 |
| IL-6(pg/ml) |
43.3±11.4 |
46.7±12.4 |
39.8±9.2 |
31.4±8.5a |
34.3±9.2 |
22.5±7.6a |
13.2±58 |
21.7±9.4a |
11.5±4.7 |
12.3±3.8 |
| CRP(mg/L) |
77.3±13.5 |
75.4±14.5 |
67.3±18.6 |
54.8±11.2a |
54.3±9.6 |
41.2±8.5a |
37.5±9.8 |
24.7±9.8a |
21.3±8.6 |
19.7±6.4 |
aP<0.05
vs control.
Table
3 Changes
of serum amylase, urine amylase and CT scores in two groups
|
1
d |
4
d |
7
d |
11
d |
15
d |
|
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
| Serum
amylase (IU) |
672±83 |
640±79 |
869±96 |
821±87 |
621±69 |
585±72 |
432±47 |
445±39 |
124±27 |
135±31 |
| Urine
amylase (IU) |
1327±324 |
1521±284 |
2227±357 |
2312±312 |
1413±315 |
1486±274 |
924±189 |
945±157 |
522±114 |
547±142 |
| CT
score |
2.5±0.8 |
2.3±0.7 |
|
|
3.8±1.1 |
3.7±0.9 |
|
|
2.1±0.5 |
2.1±0.6 |
Table
4 Changes of endotoxin concentration and L:M ratio of urine in
two groups
|
1
d |
7
d |
15
d |
21
d |
|
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
| Endotoxin
(pg/ml) |
- |
- |
5.9±1.1 |
2.4±0.7a |
8.3±3.2 |
1.9±0.8a |
8.4±1.6 |
1.7±0.6a |
| L:M |
0.047±0.019 |
0.052±0.021 |
0.097±0.023 |
0.063±0.011a |
0.143±0.046 |
0.061±0.027a |
0.156±0.032 |
0.057±0.028a |
aP<0.05
vs control.
Table
5 Changes
of CD4:CD8 ratio and IgG concentration in two groups
|
1
d |
7
d |
15
d |
21
d |
|
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
Control |
Treatment |
| CD4:CD8 |
1.82±0.02 |
1.85±0.04 |
1.54±0.05 |
1.72±0.06a |
1.64±0.07 |
1.82±0.04a |
1.78±0.03 |
1.87±0.05a |
| IgG
(mg/L) |
12.3±1.7 |
11.8±1.1 |
9.8±0.9 |
11.4±0.7 |
10.8±0.6 |
11.8±0.7a |
11.0±0.5 |
12.2±0.6a |
aP<0.05
vs control.
DISCUSSION
Infected pancreatic necrosis is the most severe complication in
patients with SAP. Its occurrence is associated with systemic
inflammatory response syndrome (SIRS), sepsis, and multiple organ
failure (MOF). Failure of intestinal barrier function is probably
responsible for the occurrence of these phenomena [16-19].
Experimental models have shown that infection of necrotic pancreas
is caused by translocated intestinal bacteria. Bacterial endotoxins
and antigens invade the portal circulation and generate cytokines,
causing multiple organ failure syndrome (MODS). Enteral feeding has
been proved to be beneficial in burn patients and major trauma
victims. Theoretically, EN should help preserve intestinal barrier
function in patients with SAP[20-23].
It is worth considering which factors contribute to the
failure of gut barrier function in acute pancreatitis. Some of these
factors are consequences of the disturbance of peristalsis caused by
paralysis and disturbance of perfusion caused by hypotension. The
most important factor is the deficiency of oxygen and substrate
supply for enteric mucosae. Atrophy and apoptosis of intestinal
mucosae occur after several days of PN, and the permeability of
intestinal wall increases[24-26]. The increased
permeability of intestinal wall allows macromolecules, bacteria,
endotoxins, and antigens to enter into the portal circulation and
adjacent tissues. This invasion elicits an inflammatory response by
stimulating the macrophages and neutrophil granulocytes and by
inflammatory cytokines (IL-1, 2, and 6 and TNF). These inflammatory
mediators may be responsible for the development of SIRS and MODS[27-29].
Our study indicated that inflammatory mediators (CRP, IL-6 and TNF-a)
in the treatment group decreased earlier (on the 4th day)
than those in the control group (on the 7th day).
Similarly, APACH II scores in the treatment group declined earlier
(on the 7th day) than those in the control group (on the
11th day). These results suggest that the combined
therapy of EN and PN could avoid the excess production of
inflammatory mediators, and then alleviate SIRS and acute phase
response.
Glutamine is an amino acid rich in the plasma and
intracellular free amino acid pool. It is essential for a wide
variety of physiologic processes, in particular, the growth and
function of enteric mucosae and immune cells including lymphocytes
and macrophages[30-32]. In SAP, glutamine is in condition
of excess utilization and endogenous glutamine production may not
adequate. In our present study, glutamine was added into the
elements of PN and EN. The results showed that endotoxin
concentration and urine L:M ratio in the treatment group did not
have any change, but elevated markedly in the control group. It was
indicated that intestinal epithelial cells and immune cells received
nutrients especially glutamine from the gut and reins in the
treatment group. Furthermore, intestinal motility adjusted the
secretion of enteral hormones and enhanced blood flow. Therefore,
the combined therapy of PN and EN can prevent mucosae from atrophy
and apoptosis effectively. Meanwhile, the results of CD4:CD8 ratio
of T cells and serum IgG concentration indicated that the immune
function in the treatment group was protected effectively. The
combined therapy of PN and EN protected mucosal barrier and immune
function, which could prevent the translocation of bacteria
effectively.
Several investigations have emphasized that early EN should
be beneficial to patients with SAP. However, too early EN or
intragastric nutrition would increase the exocrine of pancreas,
which aggravates pancreatitis. Our criteria for the enteral feeding
are to alleviate the acute phase response, stabilize the organs
function and limit the local necrosis tissue and exudates.
Nutritional tube must be placed in the superior segment of jejunum,
so enteric feeding will not increase the amount of pancreatic
secretions[33, 34]. Because the gut failed to function in
patients with SAP and the nutritional tube couldnot peristalsize,
the tube should be pushed with endoscopy or under X-ray to the
superior segment of the jejunum[35]. In this study, CT
scores and the concentration of amylase indicated that EN did not
simulate the excretion of pancreas, and thus could avoid
exaggerating the inflammation of pancreas.
In summary, the results of our study provide evidences that
combined therapy of EN and PN can significantly modulate acute phase
response and improve the mucosal barrier and immune defense. Thus,
appropriate application of PN and EN appears to be more effective
for patients with SAP.
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Edited
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