Severe Acute Pancreatitis

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JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 9, No. 4 - July 2008. [ISSN 1590-8577] 440

ORIGINAL ARTICLE

Nasogastric Tube Feeding in Predicted Severe Acute Pancreatitis.

A Systematic Review of the Literature to Determine Safety and Tolerance

Maxim S Petrov1

, M Isabel TD Correia2

, John A Windsor3

1

Department of Surgery, Nizhny Novgorod State Medical Academy. Nizhny Novgorod, Russia.

2

Department of Surgery, Federal University of Minas Gerais. Belo Horizonte, Brazil. 3

Department

of Surgery, University of Auckland. Auckland, New Zealand

ABSTRACT

Context Nasogastric tube feeding is safe and

well tolerated in most critically ill patients.

However, its safety and tolerance in the

setting of severe acute pancreatitis is

debatable.

Objective We aimed to review all available

studies on nasogastric feeding in patients with

severe acute pancreatitis to determine the

safety and tolerance of this approach. A

further aim was to perform a meta-analysis of

the available randomized controlled trials

regarding nasogastric versus nasojejunal

feeding.

Methods Three electronic databases

(Cochrane Central Register of Controlled

Trials, EMBASE and MEDLINE) and the

abstracts of major gastroenterological

meetings were reviewed. Meta-analysis was

performed using the random effects model.

Main outcome measures The summary

estimates were reported as risk ratio (RR)

with 95% confidence interval (95% CI).

Results A total of four studies on nasogastric

tube feeding in 92 patients with predicted

severe acute pancreatitis were identified.

Documented infected pancreatic necrosis

developed in 11 patients (16.9%) and multiple

organ failure in 10 (15.4%) out of 65 patients

with available data. Overall, there were 15

deaths (16.3%). An exacerbation of pain after

initiation of feeding occurred in 3 (4.3%) out

of 69 patients with available data. Full

tolerance was achieved in 73 (79.3%) patients

who did not require temporary reduction,

stoppage or withdrawal of nasogastric

feeding. The results of nasogastric feeding as

compared to nasojejunal feeding, were no

worse in terms of mortality (RR=0.77; 95%

CI: 0.37 to 1.62; P=0.50) or intolerance of

feeding (RR=1.09; 95% CI: 0.46 to 2.59;

P=0.84).

Conclusion Nasogastric feeding appears safe

and well tolerated in patients with predicted

severe acute pancreatitis. An adequately

powered randomized trial on nasogastric

versus nasojejunal feeding is required to

support this approach as routine clinical

management.

INTRODUCTION

Nutritional support plays an important role in

the management of patients with severe acute

pancreatitis [1, 2, 3]. It has been convincingly

demonstrated in numerous studies that enteral

nutrition is preferable to parenteral nutrition

as it leads to significantly better glycemic

control and decreases infectious complications and mortality [4, 5, 6, 7]. With these

apparent benefits, the question has been to

determine the most optimal site of tube

feeding administration. The alternatives

include nasojejunal and nasogastric tube

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placement. The former requires the assistance

of an endoscopist or a radiologist which may

result in a delay in commencing enteral

nutrition. This delay may have an impact on

the clinical outcome as it is now believed that

enteral nutrition should commence as soon as

possible after hospital admission in order to

maximize clinical benefits [8]. In contrast, a

nasogastric feeding tube can be inserted

immediately and with ease so that pre-pyloric

feeding can be started without delay.

A number of randomized controlled trials

(RCTs) and the latest meta-analysis [9] have

demonstrated the equivalence of nasogastric

and nasojejunal tube feeding in terms of

safety and tolerance in critically ill patients.

While this may be true for this group of

patients in general, it is recognized that

patients with severe acute pancreatitis are

particularly prone to gastric ileus because of

the subjacent inflamed pancreas [10]. This has

been given as a reason for providing enteral

nutrition into the jejunum [1, 11]. Another

reason given to avoid the provision of enteral

nutrition proximal to the jejunum has been the

concern that pancreatic exocrine stimulation

will result in an increased severity of the

acute pancreatitis [12]. Most studies reveal

that the majority of patients receiving enteral

nutrition for severe acute pancreatitis have

received nasojejunal tube feeding, but there

are some studies of successful nasogastric

feeding [13, 14, 15].

The only review on nasogastric feeding in

acute pancreatitis [16] attempted to define the

feasibility of this route of nutrition by metaanalyzing the data from RCTs on nasogastric

versus ‘conventional’ nutrition. The pooled

estimates and variance of the treatment effect

were based on the statistical aggregation of

the results from studies with essentially

different comparators (i.e., total parenteral

and nasojejunal tube feeding). Such an

approach might be misleading as nasojejunal,

but not parenteral, nutrition is now considered

the therapy of choice in severe acute

pancreatitis. Moreover, there was a marked

heterogeneity in baseline risk among the

studies involved in that meta-analysis,

particularly in regards to age and gender ratio

[15, 17], and incorrect pooled estimates were

presented due to inaccurate data input [14,

15]. Furthermore, the previous review [16]

did not determine the efficacy of nasogastric

tube feeding alone.

The aim of this systematic review was to

assess the relative efficacy of nasogastric

versus nasojejunal feeding in severe acute

pancreatitis, and to determine the safety and

tolerance of nasogastric tube feeding. This

was done by analyzing all of the literature

(randomized and non-randomized studies)

relating to acute pancreatitis and nasogastric

tube feeding.

METHODS

A computerized literature search of the

Cochrane Central Register of Controlled

Trials, EMBASE and MEDLINE through

December 1st, 2007 was conducted. The key

words for Cochrane Central Register of

Controlled Trials were “acute pancreatitis”

and “nutrition”. The key words for EMBASE

included the terms “acute pancreatitis” and

“enteral nutrition” or “enteral feeding”. The

same key words used for EMBASE were used

for MEDLINE. No language restrictions were

applied. The bibliographies of all selected

articles found which included information on

nasogastric tube feeding in acute pancreatitis

were reviewed in an attempt to find other

relevant articles. The abstracts of major

pancreatology meetings (Digestive Disease

Week (DDW), United European Gastroenterology Week (UEGW), International

Hepato-Pancreato-Biliary Association (IHPBA),

and European Pancreatic Club (EPC)) until

2007 were also manually screened.

The following selection criteria were used to

identify published studies for inclusion in this

systematic review: study design: cohort study

or RCT; population: patients with predicted

severe acute pancreatitis; intervention:

nasogastric tube feeding; outcome: at least

one of the following: tolerance, organ failure,

infectious complications, and mortality.

The records extracted by the initial search

were scanned to exclude obviously irrelevant

studies. Full-text articles were retrieved and

reviewed by two authors (MSP, MITDC)

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independently with the aim of applying

inclusion criteria. All differences found

between the two reviewers were resolved by

discussion among the three authors of this

paper.

The methodological quality of the randomized

studies included was estimated using a

modification of the previously published

quality score [18]. It consists of 8 parameters

with a quality score range from 0 to 16 points

(Table 1).

Chosen a priori, a meta-analysis (Review

Manager - RevMan (Computer program);

Version 5.0. Copenhagen, The Nordic

Cochrane Centre, The Cochrane Collaboration, 2008) was carried out on the data from

the RCTs of nasogastric versus nasojejunal

feeding. The outcome data were combined to

determine the risk ratio (RR), with its 95%

confidence interval (95% CI). The presence of

heterogeneity was assessed using the I2

measure, with I2

greater than 25% indicating

significant heterogeneity [19]. Irrespective of

the degree of heterogeneity of effect among

the trials included, a random effects model

was used.

RESULTS

A total of 396 publications were identified

using the above-mentioned search strategy.

Of these, 392 articles did not meet the

inclusion criteria and were subsequently

excluded. Figure 1 details the selection

process. A total of 4 studies were included in

Table 1. Methodological quality score.

Criteria Score

Selection - Random patients

- Consecutive patients

- Selected patients or not reported

2

1

0

Baseline

comparability

- Groups comparable on 5-6 items

- Groups comparable on 3-4 items

- Groups comparable on 0-2 items

Items:

Age: mean (median) differs <10%

Sex: proportion of men differs <10%

Aetiology: biliary and/or alcohol differs <10%

Severity score on admission: mean (median) differs <10%

CRP concentration on admission: mean (median) differs <10%

Time between onset of symptoms and commencement of treatment differs <10%

2

1

0

Patients

Withdrawals - No

- <10%

- >10% or not reported

2

1

0

Concealment of

allocation

- Adequate concealment

- Inadequate concealment

- No concealment or not reported

2

1

0

Method of

allocation

- Valid randomization

- Quasi-randomization

- No randomization or not reported

2

1

0

Blinding - Double-blind

- Single-blind

- Unblinded or not reported

2

1

0

Protocol of

intervention

- Reproducibly reported

- Poorly reported

- Not reported

2

1

0

Intervention

Co-interventions - Reported and equal between groups

- Reported but not equal between groups

- Not reported

2

1

0

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this review [13, 14, 15, 17]. One study was a

cohort study [13] whereas the other three

studies were RCTs [14, 15, 17]. The control

groups for the RCTs were nasojejunal feeding

in two [14, 15] and parenteral feeding in the

third one [17]. Table 2 demonstrates the

characteristics of the studies included in this

systematic review, including the assessment

of study quality. Overall, 93 patients with

predicted severe acute pancreatitis were

enrolled in these trials. The severity of the

patients at admission was comparable in all 4

cohorts, based on APACHE II scoring. Table

3 presents the baseline characteristics of the

patients who received nasogastric tube

feeding. One patient had a protocol violation;

therefore, the results were available in 92

patients (the characteristics of the protocol

violator are unknown).

The main clinical outcomes of the studies are

summarized in Table 4. Thirty-five of the 92 Figure 1. Selection of eligible studies.

Table 2. Characteristics of the studies included.

Study Setting Design Control

group

APACHE II

score

Feeding

start

Feeding

formula

Duration of

nutrition

(days)

Quality of

the study c

Eatock et al.,

2000 [13]

UK Cohort

study

N/A 10 (4-28) a

admission

Semielemental

Not stated N/A

Eatock et al.

2005 [14]

UK RCT Nasojejunal 10 (7-18) a

onset

Semielemental

5 14

Kumar et al.

2006 [15]

India RCT Nasojejunal 10.5±3.8 b

48-72 h of

admission

Semielemental

7 13

Eckerwall et al.,

2006 [17]

Sweden RCT Parenteral 10 (8-13) a

admission

Polymeric 6 (5-9) a 14

a

Values are median (range)

b

Values are mean ± standard deviation c

The range of the quality score is 0 to16 (Table 1)

Table 3. Characteristics of patients receiving nasogastric tube feeding.

Study No. of Etiology

patients

Age

(years)

Male:female

ratio Biliary Alcohol Other

Eatock et al., 2000 [13] 26 47 (27-96) a 12:14 18 5 3

Eatock et al., 2005 [14] 27 63 (47-74) a 14:13 16 6 5

Kumar et al., 2006 [15] 16 43.3±12.8 b 14:2 8 4 4

Eckerwall et al., 2006 [17] c 24 71 (58-80) a 10:14 14 3 7

Total c 93 - 50:43 56 18 19 a

Values are median (range)

b

Values are mean ± standard deviation c

Before exclusion of one protocol violator

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patients (38.0%) required ventilatory support.

There was no evidence of aspiration

pneumonia in any of the patients. The other

outcomes were available in 3 studies only (65

cases): infected pancreatic necrosis was

revealed in 11 patients (16.9%), multiple

organ failure developed in 10 patients

(15.4%), and 12 patients underwent surgery

(18.5%). The mortality rate was 16.3% (15

cases).

Nasogastric feeding-related outcomes,

including safety and tolerance, are presented

in Table 5. Full tolerance was achieved in 73

of the 92 (79.3%) patients who did not require

temporary reduction, stoppage or withdrawal

of nasogastric feeding. The 19 patients who

had a modification of the nasogastric tube

feeding regimen presented signs of gastric

ileus (n=6), diarrhea (n=10), or repeatedly

removed their feeding tube (n=3). Three

patients out of 69 (4.3%) experienced an

exacerbation of pain after commencement of

nutrition, although it was not a reason for the

discontinuation of tube feeding in any of the

cases.

The meta-analysis was restricted to the

randomized studies of nasogastric versus

nasojejunal feeding. In two eligible trials [14,

15], a total of 43 patients received enteral

nutrition via the nasogastric route and 36

patients via the nasojejunal route. The use of

nasogastric feeding resulted in a nonsignificant reduction in the risk of death

(RR=0.77; 95% CI: 0.37 to 1.62; P=0.50)

(Figure 2). The number of nutritionassociated adverse events was similar

Table 4. Outcomes of nasogastrically-fed patients in the studies included.

Study No. of

patients

Patients on

ventilatory

support

Patients

with MOF

Infected

pancreatic

necrosis

Surgery Mortality LOS

(days)

Eatock et al., 2000 [13] 26 11 (42.3%) 6 (23.1%) 5 (19.2%) 10 (38.5%) 4 (15.4%) 17.5 (3-82) a

Eatock et al., 2005 [14] 27 7 (25.9%) Not stated Not stated Not stated 5 (18.5%) 16 (10-22) a

Kumar et al., 2006 [15] 16 15 (93.8%) 3 (18.8%) 5 (31.3%) 1 (6.3%) 5 (31.3%) 24.1±14.4 b

Eckerwall et al., 2006 [17] 23 2 (8.7%) 1 (4.3%) 1 (4.3%) 1 (4.3%) 1 (4.3%) 9 (7-14) a

Total 92 35/92

(38.0%)

10/65

(15.4%)

11/65

(16.9%)

12/65

(18.5%)

15/92

(16.3%)

-

a

Values are median (range)

b

Values are mean ± standard deviation

LOS: length of hospital stay

MOF: multiple organ failure

Table 5. Tolerance of nasogastric tube feeding in the studies included.

Study No. of

patients

Diarrhea Tube

removal

Gastric

retention

Exacerbation of

pain following

feeding

Achievement of

nutritional goal

Full

tolerance of

feeding a

Eatock et al., 2000 [13] 26 3 (11.5%) 1 (3.8%) 3 (11.5%) 0 Not stated 19 (73.1%)

Eatock et al., 2005 [14] 27 3 (11.1%) 1 (3.7%) 0 2 (7.4%) 21 patients

(77.8%) after 60 h

23 (85.1%)

Kumar et al., 2006 [15] 16 4 (25%) 1 (6.3%) 0 1 (6.3%) 16 patients

(100%) by day 7 b

11 (68.8%)

Eckerwall et al., 2006 [17] 23 0 0 3 (13%) Not stated 15 patients

(65.2%) by day 7

20 (86.9%)

Total 92 10/92

(10.9%)

3/92

(3.3%)

6/92

(6.5%)

3/69

(4.3%)

52/66

(78.8%)

73/92

(79.3%) a

Did not require temporary reduction, stoppage or withdrawal of feeding

b

Six patients were supplemented by parenteral nutrition during the commencement of feeding

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between the two groups. As a consequence,

nasogastric feeding was associated with nonsignificant increases in the risk of diarrhea

(RR=1.42; 95% CI: 0.46 to 4.38; P=0.54)

(Figure 3) and the exacerbation of pain

following feeding (RR=1.74; 95% CI: 0.24 to

12.79; P=0.58) (Figure 4). Overall, patients in

both groups did not differ significantly in

terms of an intolerance to feeding (RR=1.09;

95% CI: 0.46 to 2.59; P=0.84) (Figure 5).

There was no heterogeneity between the study

results for all comparisons (I2

=0%).

DISCUSSION

This systematic review of the literature

demonstrates the safety and tolerance of

nasogastric tube feeding in 4 out of 5 patients

with predicted severe acute pancreatitis. The

clinical outcomes were within the expected

range. Nasogastric tube feeding-related

problems occurred in about 20% of patients,

but they were relatively minor. The metaanalysis also demonstrated that there was no

difference between nasogastric and

nasojejunal tube feeding with respect to safety

and tolerance in the two available RCTs.

However, there were limitations in both the

RCTs. Some data on certain essential clinical

outcomes were not presented in the RCT from

the United Kingdom [14]. In addition, it was

noted that it is likely that jejunal tube feeding

in this trial was probably duodenal (because

Figure 2. Random effects model of the risk ratio of death associated with nasogastric feeding in comparison with

nasojejunal feeding.

Figure 3. Random effects model of the risk ratio of diarrhea associated with nasogastric feeding in comparison with

nasojejunal feeding.

Figure 4. Random effects model of the risk ratio of pain exacerbation associated with nasogastric feeding in

comparison with nasojejunal feeding.

Figure 5. Random effects model of the risk ratio of intolerance of feeding associated with nasogastric feeding in

comparison with nasojejunal feeding.

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true jejunal placement would have been

difficult with the types of feeding tubes and

placement techniques used) meaning that both

feeding arms may have been equally proinflammatory [20]. The defect of the RCT

from India [15] was that there was a

considerable delay (7.8±6.5 and 5.7±4.7 days

after symptom onset in the nasogastric and

nasojejunal groups, respectively) in

commencing enteral nutrition. Apart from

these concerns, both trials were insufficiently

powered to detect any difference or to prove

equivalence between the groups studied in

terms of any clinical outcome. For example,

an adequately powered RCT would need to

enrol 153 patients per arm in order to show a

decrease in mortality from 16% (average rate

in the nasogastric group in the present review)

to 6% (best results in the nasojejunal group of

RCTs on enteral versus parenteral nutrition

[21, 22]) with 80% power and alpha value

equal to 0.05 (two-sided).

One of the most important issues in

considering tube feeding in acute pancreatitis

is the effect of nutrition on pancreatic

exocrine function. It was shown by O’Keefe

et al. [23] that all forms of enteral nutrition

stimulate pancreatic secretion. In particular,

when compared to placebo-saline, an oral

liquid polymeric diet resulted in a

significantly higher level of amylase (P<0.01)

and lipase (P<0.01); a duodenal polymeric

enteral formula led to an increased level of

amylase (P<0.01), lipase (P<0.01) and trypsin

(P<0.01); a duodenal elemental feeding

formula resulted in an elevated level of lipase

(P<0.05). The same research group also

compared pancreatic secretory response to

tube feeding delivered into the duodenum,

mid jejunum (40-60 cm distal to the ligament

of Treitz), and distal jejunum (100-120 cm

distal to the ligament of Treitz) [24]. Even

though the authors did not find a direct

relationship between the decrease in enzyme

secretion and the distance to the mid-distal

jejunum, they demonstrated a significantly

lower secretion of trypsin (P<0.01) and lipase

(P<0.05) in response to the elemental formula

delivered into the jejunum (40 cm or more

distal to the ligament of Treitz) in comparison

with the duodenum. Moreover, the trypsin

and lipase secretory response in the mid-distal

jejunum group was as low as in the control

group (fasting).

It should be noted, however, that these studies

[23, 24] on the effects of enteral feeding on

pancreatic exocrine function were in healthy

subjects. There is now convincing evidence

[25] that patients with acute pancreatitis have

significantly lower rates of pancreatic enzyme

secretion into the duodenum as compared to

healthy subjects. Furthermore, when patients

with mild/moderate acute pancreatitis were

compared to those with severe acute

pancreatitis, a lower secretion of trypsin (6-

fold), amylase (22-fold) and lipase (42-fold)

was found in the latter group, suggesting that

duodenal secretion of pancreatic enzymes is

inversely related to the severity of acute

pancreatitis [25]. In line with this finding,

another study [26] showed 86% rate of

pancreatic exocrine insufficiency (measured

by fecal pancreatic elastase-1) in patients

recovering from severe attacks of acute

pancreatitis. Moreover, the severity of

pancreatic exocrine insufficiency correlated

with the extent of pancreatic necrosis. These

data suggest that injured acinar cells are not

able to fully respond to the physiological

stimuli of secretion into the duodenum and

this may be of some help in explaining the

findings of this review, namely, that

nasogastric tube feeding does not appear to

aggravate the severity of acute pancreatitis.

In conclusion, the present review has

appraised the current evidence regarding

nasogastric tube feeding to patients with

predicted severe acute pancreatitis. The

evidence base is small but does show that

enteral nutrition administered by means of the

nasogastric route is safe and well tolerated in

79% of patients with predicted severe acute

pancreatitis. The statistically aggregated data

from two randomized trials on the direct

comparison of nasogastric and nasojejunal

nutrition are encouraging as they demonstrate

no difference in safety and tolerance between

these routes. An adequately powered

randomized trial on nasogastric versus

nasojejunal feeding is required to support this

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approach before early nasogastric tube

feeding can be established as the standard of

care.

Received January 28th, 2008 - Accepted April

15th, 2008

Keywords Enteral Nutrition; Pancreatitis,

Acute Necrotizing /complications

Abbreviations RCT: randomized controlled

trials

Conflict of interest The authors have no

potential conflicts of interest

Correspondence

Maxim S Petrov

PO Box 568

Nizhny Novgorod

603000 Russia

Phone: +7-910.383.3963

Fax: +1-801.788.7383

E-mail: max.petrov@gmail.com

Document URL: http://www.joplink.net/prev/200807/04.html

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