Selective decontamination of the gastrointestinal tract in patients undergoing esophageal resection.

Abstract

Selective decontamination of the digestive tract (SDD) to eliminate gram-negative bacteria is still not widely accepted, although it reduces the incidence of nosocomial infections. In a previous retrospective study, a clear benefit to perioperative morbidity, and a reduction in nosocomial infections were found in patients who underwent an esophageal anastomosis. Thus, SDD was applied routinely for esophageal anastomoses. We report the outcome of a cohort of 81 patients who underwent this treatment.
From 2002, patients who underwent an esophageal anastomosis (esophagojejunostomy) were prospectively recorded. Perioperatively, patients received polymyxin, tobramycin, vancomycin and nystatin by mouth four times a day. Outcome was compared to a control group that was treated before 2002 (68 patients without SDD and 53 patients with SDD). Postoperative morbidity and mortality were assessed.
Between 2002 and 2007, 81 patients who underwent an esophageal anastomosis received SDD. Compared to a retrospective control group, patients with SDD had significantly less pneumonia (OR 0.06 (0.01-0.46), p < 0.001) and lower morbidity (OR 0.16 (0.05-0.49), p < 0.001). Furthermore, fewer anastomotic insufficiencies and complications were found. Similar results were found in the analysis of the patients treated before 2002.
SDD significantly reduces perioperative morbidity and mortality in patients who undergo a distal esophageal anastomosis compared to a historical control group. In patients with an anastomotic leakage, there was a strong tendency of SDD to reduce postoperative mortality.

Full text

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RESEARCH ARTICLEOpen Access
Selective decontamination of the gastrointestinal
tract in patients undergoing esophageal resection
Franziska Näf†, René Warschkow†, Walter Kolb, Michael Zünd, Jochen Lange, Thomas Steffen*
Abstract
Background: Selective decontamination of the digestive tract (SDD) to eliminate gram-negative bacteria is still not
widely accepted, although it reduces the incidence of nosocomial infections. In a previous retrospective study, a
clear benefit to perioperative morbidity, and a reduction in nosocomial infections were found in patients who
underwent an esophageal anastomosis. Thus, SDD was applied routinely for esophageal anastomoses. We report
the outcome of a cohort of 81 patients who underwent this treatment.
Methods: From 2002, patients who underwent an esophageal anastomosis (esophagojejunostomy) were
prospectively recorded. Perioperatively, patients received polymyxin, tobramycin, vancomycin and nystatin by
mouth four times a day. Outcome was compared to a control group that was treated before 2002 (68 patients
without SDD and 53 patients with SDD). Postoperative morbidity and mortality were assessed.
Results: Between 2002 and 2007, 81 patients who underwent an esophageal anastomosis received SDD.
Compared to a retrospective control group, patients with SDD had significantly less pneumonia (OR 0.06 (0.01-
0.46), p < 0.001) and lower morbidity (OR 0.16 (0.05-0.49), p < 0.001). Furthermore, fewer anastomotic insufficiencies
and complications were found. Similar results were found in the analysis of the patients treated before 2002.
Conclusions: SDD significantly reduces perioperative morbidity and mortality in patients who undergo a distal
esophageal anastomosis compared to a historical control group. In patients with an anastomotic leakage, there
was a strong tendency of SDD to reduce postoperative mortality.
Background
After the introduction of selective decontamination of
the digestive tract (SDD) in intensive care unit patients in
1984, a reduction in the incidence of nosocomial infec-
tions in patients with endotracheal tubes was shown [1].
Prophylactic perioperative SDD to prevent nosocomial
infection in patients undergoing an esophageal anasto-
mosis is effective and easy to perform [2]. Topical appli-
cation of nonresorbable antimicrobial agents to the
oropharynx and gastrointestinal tract typically prevents
secondary colonization with Gram-negative bacteria,
S. aureus and yeast. Only selective antibiotics (both topi-
cally and systemically) without anti-anaerobic activity are
usually used to maintain the anaerobic intestinal flora.
These measures reduce the incidence of perioperative
nosocomial infections [3-7]. Furthermore, SDD has been
shown to be effective in the prevention of esophagojeju-
nal anastomotic leakage after total gastrectomy and has
therefore been proposed as a prophylactic measure
[2;8;9]. However, SDD has not yet been widely accepted
as standard procedure for patients undergoing an eso-
phageal anastomosis, which represents a group of
patients with relatively high risk of perioperative morbid-
ity. Pulmonary complications are the major source of
morbidity and mortality after esophageal resection [10].
Approximately 30% of patients who undergo esophagec-
tomies suffer from respiratory complications, and 80% of
these complications occur within the first five postopera-
tive days [11].
Several risk factors for pulmonary infections in
patients who undergo esophagectomies were identified.
Elderly patients and those with chronic obstructive pul-
monary disease are at risk for the development of major
pulmonary complications that require interventions,
such as antibiotic therapy, bronchoscopy or endotra-
cheal intubation. Pneumonia is frequently caused by
* Correspondence: Thomas.Steffen@kssg.ch
† Contributed equally
Department of Surgery, Kantonsspital St. Gallen (KSSG), CH-9007, St. Gallen,
Switzerland
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postoperative aspiration and is the major cause of death
in these patients. Minor pulmonary complications that
do not require interventional measures occur in almost
all patients who undergo an esophageal resection [12].
Leakage of the esophageal anastomosis is another ser-
ious and potentially life-threatening complication.
Together with postoperative pulmonary infections, ana-
stomotic leakage is a major cause of death after esopha-
geal resection [13].
Based on these findings and experiences with intensive
care unit patients, SDD was introduced at our hospital
as perioperative prophylaxis in patients undergoing an
esophageal anastomoses, in a manner analogous to the
approach described in Schardey et al. [2]. The intention
was to reduce the incidence of postoperative infections
and therefore reduce perioperative morbidity and
mortality.
In a previously analyzed retrospective cohort, we
showed a reduction in postoperative nosocomial infec-
tions in patients with SDD compared to patients with-
out SDD (data not published at the time). Based on
these positive results, SDD was routinely implemented
as perioperative prophylaxis for all patients undergoing
an esophageal anastomosis. Consequently, all patients
receiving a total or partial esophagectomy, transhiatal
esophagogastrectomy or a total gastrectomy were con-
sistently treated with SDD; data were prospectively
recorded to determine the perioperative morbidity and
mortality (especially in patients who developed an ana-
stomotic leakage) compared to a retrospective control
group.
The aim of this study was to determine whether there
was a benefit of SDD to postoperative morbidity and
mortality in patients undergoing an esophageal anasto-
mosis. For this purpose, the results of our prospective
cohort were compared to the previously analyzed retro-
spective cohort of surgical patients at our institution
who did not receive SDD.
Methods
Between January 2002 and December 2007, a total of
124 patients underwent elective partial or total esopha-
geal resection at a tertiary referral hospital, and data
were prospectively recorded and retrospectively ana-
lyzed. All patients undergoing an esophageal anastomo-
sis after either total gastrectomy, transhiatal extended
gastrectomy or a Merendino procedure were included in
the study [14]. Patients who underwent the following
procedures were excluded (n = 43): those who under-
went a transthoracic esophagectomy were excluded
because they had a cervical anastomosis and no
intrathoracic anastomoses; patients having a subtotal
gastrectomy with pouch reconstruction were excluded
because a gastrojejunostomy was considered to be a
different procedure. Additionally, patients undergoing a
transmediastinal esophagectomy were excluded to sepa-
rate proximal esophageal anastomoses from distal eso-
phageal anastomoses because we believe these groups
differ in terms of anastomotic leakage. Thus, a homoge-
neous cohort of 81 consecutive patients undergoing an
esophageal anastomosis remained for further analyses.
For SDD, patients received a solution of polymyxin
(100 milligrams), tobramycin (80 milligrams), vancomy-
cin (125 milligrams) and nystatin (500 milligrams) by
mouth four times a day. This solution was administered
at a dose of 10 milliliters by mouth every six hours, and
the treatment was continued intraoperatively and post-
operatively via a gastric tube. The treatment was started
on the morning of the day before surgery (they received
at least four doses before surgery) and continued until
the seventh postoperative day. All patients received total
parenteral nutrition postoperatively for 7 days. On post-
operative day 7, a radiological imaging study with oral
water-soluble contrast was routinely performed to deter-
mine whether anastomotic leakage occurred. Anastomo-
tic leakage was defined as an extravasation of the water-
soluble contrast during the radiological study. If the
radiological test was normal, the patients were allowed
to start oral intake and SDD was stopped on day 7.
Total parenteral nutrition was reduced when solid oral
intake was started, which was usually on postoperative
day 9. Pulmonary infection was diagnosed if two or
more of the following clinical signs were present: fever,
lung infiltrates on radiological imaging studies, purulent
respiratory secretion or a positive culture from respira-
tory secretions. If a pulmonary infection was diagnosed,
it was treated with tazobactam-piperacillin according to
the hospital guidelines for the treatment of nosocomial
pulmonary infections. All patients with suspected pul-
monary infections underwent chest radiography to con-
firm the diagnosis.
All patients (retrospective and prospective, with or with-
out SDD) received perioperative antibiotic prophylaxis of
2 grams of cefamandole intravenously and 500 milligrams
of metronidazole intravenously 30 to 60 minutes before
the start of the operation, according to the hospital’s stan-
dard guidelines for perioperative antibiotic prophylaxis.
Antibiotic prophylaxis was repeated intraoperatively if the
duration of the procedure exceeded four hours.
The standard procedure for an esophageal anastomo-
sis was an end-to-side esophagojejunostomy using a 25
millimeter circular stapling device. A short, crooked
approximately 1-centimeter portion of the jejunum was
reconstructed using an ENDO GIA™ universal 45 milli-
meter stapling device.
The outcome was compared to a historic cohort (n =
121) that was treated from 1995 to 2002 at the same
institution. Within this cohort, there were two
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subgroups: one that was treated with SDD (n = 53) and
one that was not (n = 68). The surgeon chose whether
or not a patient received SDD. Since July 2002, SDD
was routinely used in all patients undergoing an esopha-
geal anastomosis (eligible for this study: n = 81). Age,
gender, body mass index (BMI), ASA score, anastomotic
leakage, pulmonary infection and mortality rate were
compared among the three groups. Perioperative mor-
bidity was analyzed using the classification described by
Dindo et al. [15].
All patients provided informed consent to the opera-
tive treatment, the administration of SDD and further
analyses of data from their medical records. The medical
ethics committee approved the analysis of these data.
Statistical analysis was performed using SPSS 11.5
software (SPSS Inc., Chicago, IL, USA). A two-sided
p-value < 0.05 was considered statistically significant.
Continuous data are expressed as mean ± standard
deviation. Confidence intervals (95% CI) of binominal
proportions were estimated according to Agresti and
Coull. Mann-Whitney U tests and Kruskal Wallis tests
were applied to compare continuous data. Chi-Square
tests were used to compare proportions.
Results
Prospective cohort: Specification of sample
Between 2002 and 2007, a cohort of 81 patients who
underwent an esophageal anastomosis (esophagojeju-
nostomy) and received SDD was obtained. A total gas-
trectomy was performed in 41 patients (51%), transhiatal
esophagogastrectomy was performed in 26 (32%)
patients and a Merendino procedure was performed in
14 (17%) (14). The mean patient age was 63.1 ± 11.5
years; this cohort included 47 (58%) women.
Comparability of groups
In Table 1, baseline characteristics of both the prospec-
tive and retrospective groups are provided. No
significant differences in age, BMI or ASA classification
were found between the three groups.
Retrospective analysis (Table 2)
Patients from the retrospective subgroup with SDD were
compared to patients who had no SDD. Significantly
fewer patients with SDD than those without SDD died
within the first 30 postoperative days. A mortality rate
of 17.6% (12/68; 95% CI 10.2% - 28.5%) was found in
the retrospective subgroup without SDD compared to
the mortality rate of 1.9% (1/53; 95% CI 0.3% - 13.5%)
in the subgroup with SDD (p = 0.005). Of the patients
without SDD, 13.2% (9/68; 95% CI 6.9% - 23.5%) devel-
oped an anastomotic leakage, whereas only 3.8% (2/53;
95% CI 0.3% - 13.5%) of the retrospective subgroup with
SDD developed an anastomotic leakage (p = 0.072). Of
the patients who had no SDD, 25.0% (17/68; 95% CI
16.2% - 36.5%) developed postoperative pneumonia
compared to 11.3% (6/53; 95% CI 4.9% - 22.9%) of the
patients with SDD (p = 0.057). The postoperative length
of hospital stay was shorter in the retrospective
subgroup with SDD (21.8 ± 13.7 vs 25.2 ± 18.0 days,
p = 0.145). According to the Dindos classification,
overall morbidity was less severe in patients with SDD
(p = 0.009) (Table 3).
Longitudinal analysis
The retrospective subgroup with SDD was compared to
the prospective cohort with SDD (Table 2), and no sta-
tistically significant differences were found in terms of
30-day mortality: 1.9% (1/53; 95% CI 0.0% - 10.9%) in
the retrospective subgroup compared to 1.2% (1/81; 95%
CI 0.0% - 7.3%) in the prospective cohort (p = 0.761). In
the retrospective subgroup, 11.3% (6/53; 95% CI 4.9% -
22.0%) developed postoperative pneumonia compared to
4.9% (4/81; 95% CI 1.6% - 12.4%) in the prospective
cohort (p = 0.169). In the retrospective subgroup with
SDD, 3.8% (2/53; 95% CI 0.3% - 13.5%) developed an
anastomotic leakage, whereas 7.4% (6/81; 95% CI 3.2% -
15.5%) suffered from anastomotic leakage in the pro-
spective cohort (p = 0.385). The length of postoperative
hospital stay did not differ significantly between the pro-
spective cohort and the retrospective subgroup with
SDD (20.2 ± 10.9 vs 21.8 ± 13.7 days, p = 0.861).
Patients without SDD were compared to the patients
of the prospective cohort with SDD (Table 2); the post-
operative 30-day mortality rate was significantly lower in
patients with SDD (1.2% vs. 17.6%; p = 0.001). Patients
with SDD developed pneumonia postoperatively less
often (4.9%; 4/81; 95% CI 1.6% - 12.5%) than patients
without SDD (25.0%; 17/68; 95% CI 16.2% - 36.6%; p =
0.001). Fewer patients with SDD than patients without
SDD developed an anastomotic leakage (6/81 vs. 9/68;
7.4% vs. 13.2%; p = 0.239). Patients with SDD in the
Table 1 Baseline characteristics of retrospective and
prospective groups
Retrospective no
SDD
(n = 68)
Retrospective
SDD
(n = 53)
Prospective
SDD
(n = 81)
p
valueA)
Age
[years]
63.0 ± 12.1 63.4 ± 13.0 63.1 ± 11.50.831
BMI
[kg/
m2]
23.9 ± 3.9 24.7 ± 3.7 25.0 ± 4.70.469
ASA I 4 (5.9%)
36 (52.9%)
28 (41.2%)
2 (3.8%)
34 (64.2%)
17 (32.1%)
3 (3.7%)
57 (70.4%)
21 (25.9%)
0.296
II
III
mean ± standard deviation n (percentage)
A)Kruskal Wallis test for continuous data and Chi-square test for categorical
data
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prospective cohort had significantly fewer severe compli-
cations than patients without SDD in the retrospective
subgroup (p = 0.001) (Table 3). The postoperative hos-
pital stay was shorter in the prospective cohort with
SDD than in patients without SDD (20.2 ± 10.9 vs 25.2
± 18.0 days, p = 0.046).
Pooled subgroup analysis of patients with anastomotic
leakage revealed a mortality rate of 55.6% (5/9) in the
patients without SDD compared to 12.5% (1/8) in all
patients with SDD (p = 0.064).
Discussion
This observational study corroborates the hypothesis
that SDD reduces perioperative morbidity and mortal-
ity in patients who undergo a distal esophageal anasto-
mosis [4]. In the present study, perioperative mortality
was significantly reduced in patients undergoing a dis-
tal esophageal anastomosis when perioperative SDD
was performed. Furthermore, significantly fewer
patients developed perioperative pulmonary infections.
The perioperative mortality rate of patients who post-
operatively developed an anastomotic leakage was
clearly lower in the SDD group, although this differ-
ence was not significant. However, we consider this
result to be a strong indicator of the benefit of SDD.
Anastomotic leakage is a potentially life-threatening
postoperative complication. The mortality rate in
patients with anastomotic leakage after total gastrect-
omy was reported to be as high as 45% [16]. In our
patients without SDD, a mortality rate of 55.6% was
found, whereas patients with SDD had a mortality rate
of 12.5%. Furthermore, our results are comparable to
the results of the study by Schardey et al., in which
significantlyfewerpulmonary
described, and a tendency of fewer anastomotic insuffi-
ciencies was found in patients receiving SDD [2].
infections were
Table 2 Outcome analysis
Group p value
retrospective without SDD
(n = 68)
retrospective with SDD
(n = 53)
prospective with SDD
(n = 81)
Mortality [30 days postoperative] 12 (17.6%)
(10.2% - 28.5%)
OR: 1ref)
9 (13.2%)
(6.9% - 23.5%)
OR: 1ref)
17 (25.0%)
(16.2% - 36.5%)
OR: 1ref)
25.2 ± 18.0
1 (1.9%) (0.0% - 10.9%)
OR: 0.09 (0.01-0.71)
1 (1.2%)
(0.0% - 7.3%)
OR: 0.06 (0.01-0.46)
6 (7.4%)
(3.2% - 15.5%)
OR: 0.52 (0.18-1.56)
4 (4.9%)
(1.6% - 12.4%)
OR: 0.16 (0.05-0.49)
20.2 ± 10.9
<0.001A)
Anastomotic
Leakage
2 (3.8%)
(0.3% - 13.5%)
OR: 0.26 (0.05 - 1.24)
6 (11.3%)
(4.9% - 22.9%)
OR: 0.38 (0.14-1.05)
21.8 ± 13.7
0.162A)
Postoperative
Pneumonia
0.001A)
length of hospital stay [days]0.121B)
n (percentage) (95% CI for percentage) Odds ratio (95% CI for Odds ratio)
A)Chi square tests for overall significanceB)Kruskal Wallis tests for overall significance
Closed testing procedure with chi square tests for: Mortality Leakage Pneumonia
retrospective with SDD - retrospective without SDD p = 0.005 p = 0.072 p = 0.057
prospective with SDD - retrospective without SDD p < 0.001 p = 0.239 p < 0.001
retrospective with SDD - prospective with SDD p = 0.761 p = 0.385 p = 0.169
Table 3 Classification of postoperative complications according to Dindo et al. (15)
Dindo classificationGroup
retrospective without SDD
(n = 68)
retrospective with SDD
(n = 53)
prospective with SDD
(n = 81)
grade I
grade II
grade IIIa
grade IIIb
grade IVa
grade IVb
grade V
0 (0.0%)
43 (63.2%)
6 (8.8%)
8 (11.8%)
4 (5.9%)
0 (0.0%)
7 (10.3%)
0 (0.0%)
44 (83.0%)
3 (5.7%)
3 (5.7%)
2 (3.8%)
0 (0%)
1 (1.9%)
3 (3.7%)
65 (80.2%)
5 (6.2%)
6 (7.4%)
1 (1.2%)
1 (1.2%)
0 (0.0%)
Kruskal Wallis test for overall significance: p = 0.002
Closed testing procedure with Mann Whitney U-Tests:
- retrospective with SDD vs retrospective without SDD: p = 0.009
- prospective with SDD vs retrospective without SDD: p = 0.001
- retrospective with SDD vs prospective with SDD: p = 0.819
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SDD has not been widely adopted as a prophylactic
measure in patients undergoing esophageal anastomoses.
One possible reason for this might be the fear of com-
plications of such a nonspecific antibiotic treatment. In
the studies by Tetteroo et al., no increase in antibiotic
resistance was found in patients receiving SDD found
[4-7;17]. Additionally, the most recent Cochrane review
on antibiotic prophylaxis reported no resistance asso-
ciated with SDD in one trial [18]. In the study by de
Jonge et al., a decreased development of resistance
among SDD-treated patients in intensive care over a
27-month period was reported [19]. Although not mea-
sured, SDD-associated complications in our patients sel-
dom occur; however, they most often present as nausea,
which is considered to be a mild side effect. Addition-
ally, no SDD-associated side effects were reported in a
recently published study by Roos et al. [20]. Similar
mortality rates and incidence of perioperative infections
were found when SDD was employed in patients under-
going elective colorectal surgery compared to patients
receiving the same operation but not receiving SDD.
However, in that study, SDD was not applied in a stan-
dardized fashion, and pulmonary infections were not
significantly reduced in the SDD group. We assume that
patients have recurrent micro-aspirations after esopha-
gus resection, and therefore, SDD seems to effectively
prevent the development of pulmonary infections in our
patient cohort.
We are aware of some relevant limitations of this
study. The comparison of a prospective cohort with a
retrospective cohort is problematic. However, apart
from only a few data from the literature that address
this specific problem, our retrospective patient cohort is
the only source of data available. We aimed to minimize
the risk of bias by statistically comparing all groups
where no significant differences in the baseline charac-
teristics were found. Furthermore, when comparing the
retrospective subgroups with and without SDD, essen-
tially the same outcome was obtained. However, the
absence of evidence is not evidence for absence, and
longitudinal analyses are always associated with a risk of
bias. Furthermore, we assume that advancements in
intensive care medicine and anesthesia have occurred
over the course of data collection. This possible influ-
ence on perioperative morbidity and mortality was not
addressed in the current study.
Despite the above-mentioned possible limitations of
this study, our results show a strong tendency in favor
of SDD for patients undergoing a distal esophageal ana-
stomosis. We encourage institutions where SDD is not
performed to conduct a double-blind randomized con-
trolled prospective study to obtain results regarding
SDD use with a higher level of evidence than provided
here.
Conclusions
We conclude that SDD in patients undergoing an eso-
phageal anastomosis may provide perioperative morbid-
ity and mortality benefits.
Acknowledgements
We would like to acknowledge the support of the reviewers of BMC Surgery.
Authors’ contributions
FN performed the data acquisition and drafted the manuscript. RW
participated in the study design and performed the statistical analysis. FN
and RW contributed equally to this manuscript. WK performed data
acquisition of the retrospective cohort. MZ and JL critically revised the
manuscript for important intellectual content. TS conceived the study and
participated in the study design, drafting the manuscript and performing the
revisions.
All authors read and approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 23 March 2010 Accepted: 16 December 2010
Published: 16 December 2010
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Pre-publication history
The pre-publication history for this paper can be accessed here:
http://www.biomedcentral.com/1471-2482/10/36/prepub
doi:10.1186/1471-2482-10-36
Cite this article as: Näf et al.: Selective decontamination of the
gastrointestinal tract in patients undergoing esophageal resection. BMC
Surgery 2010 10:36.
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Näf et al. BMC Surgery 2010, 10:36
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