ArticlePDF Available

Causes of Mortality in Patients With Peptic Ulcer Bleeding: A Prospective Cohort Study of 10,428 Cases

Authors:

Abstract and Figures

Despite advances in endoscopic and pharmacological treatment for peptic ulcer bleeding (PUB), mortality remains at 5-10% worldwide. Our aim was to investigate the causes of death in a prospective cohort of PUB in a tertiary referral center. Between 1993 and 2005, all patients with upper gastrointestinal bleeding (UGIB) admitted to the Prince of Wales Hospital were prospectively registered. Demographic data, characteristics of ulcer, and pharmacological, endoscopic, and surgical therapy, were documented. Mortality cases were classified as (A) bleeding-related death (A1: uncontrolled bleeding, A2: within 48 h after endoscopy, A3: during surgery for uncontrolled bleeding, A4: surgical complications or within 1 month after surgery, and A5: endoscopic related mortality) or (B) non-bleeding-related death (B1: cardiac causes, B2: pulmonary causes, B3: cerebrovascular disease, B4: multiorgan failure, and B5: terminal malignancy). In all, 18,508 cases of UGIB were enrolled; among them, 10,428 cases from 9,375 patients were confirmed to have PUB, and 577 (6.2%) patients died. There were significantly more patients who died of non-ulcer bleeding causes (79.7%) than bleeding causes (18.4%). The mean (s.d.) age of those who died of bleeding-related causes was higher (75.4 (12.6) years) than that of those who died of non-bleeding causes (71.7 (13.1) years) (P=0.010). Most bleeding-related deaths occurred when immediate control of bleeding failed (29.2%) or when patients died within 48 h after endoscopic therapy (25.5%). Among those who died of non-bleeding-related causes, multiorgan failure (23.9%), pulmonary conditions (23.5%), and terminal malignancy (33.7%) were most common. The majority of PUB patients died of non-bleeding-related causes. Optimization of management should aim at reducing the risk of multiorgan failure and cardiopulmonary death instead of focusing merely on successful hemostasis.
Content may be subject to copyright.
nature publishing group ORIGINAL CONTRIBUTIONS
STOMACH
84
The American Journal of GASTROENTEROLOGY VOLUME 105 | JANUARY 2010 www.amjgastro.com
INTRODUCTION
Although there is a general declining trend in the incidence
of peptic ulcer disease, peptic ulcer bleeding (PUB) remains
a major prevalent and clinically signi cant condition world-
wide. Recent studies suggest that the incidence of PUB ranges
from 20 to 60 per 100,000 population (1 3) , with an increasing
proportion of bleeding episodes related to the use of aspirin
and nonsteroidal anti-in ammatory drugs (NSAIDs). Despite
advances in endoscopic and pharmacological treatment in
PUB, the mortality associated with this condition stays at
around 5 – 10 % (4 – 10) . Although endoscopic therapy and adju-
vant use of proton pump inhibitors (PPIs) have been shown
to prevent recurrent bleeding, reduce the need for repeated
endoscopic therapy and surgery, and improve mortality, there
are still a substantial proportion of patients succumbing to the
bleeding episodes. One of the possible explanations is that PUB
is now predominantly a disease of the elderly, with over 60 %
of patients above the age of 60 years, and around 20 % over the
age of 80 years (11,12) . As elderly patients have more comorbid
illness, are more likely users of aspirin and NSAIDs, and are
less tolerant of hemodynamic insult, the management of this
high-risk population of PUB patient is a major challenge.
Causes of Mortality in Patients With Peptic Ulcer
Bleeding: A Prospective Cohort Study of 10,428 Cases
Joseph J.Y. Sung , MD, PhD, FRCP 1 , K e l v i n K . F . T s o i , P h D 1 , T e r r y K . W . M a , M B C h B 1 , M a n - Y e e Yu n g , B N 1 , J a m e s Y . W. L a u , M D , F R C S 1 a n d
P h i l i p W . Y . C h i u , M D , F R C S 1
OBJECTIVES: Despite advances in endoscopic and pharmacological treatment for peptic ulcer bleeding (PUB),
mortality remains at 5 10 % worldwide. Our aim was to investigate the causes of death in a
prospective cohort of PUB in a tertiary referral center.
METHODS: Between 1993 and 2005, all patients with upper gastrointestinal bleeding (UGIB) admitted to
the Prince of Wales Hospital were prospectively registered. Demographic data, characteristics of
ulcer, and pharmacological, endoscopic, and surgical therapy, were documented. Mortality cases
were classifi ed as (A) bleeding-related death (A1: uncontrolled bleeding, A2: within 48 h after
endoscopy, A3: during surgery for uncontrolled bleeding, A4: surgical complications or within
1 month after surgery, and A5: endoscopic related mortality) or (B) non-bleeding-related death
(B1: cardiac causes, B2: pulmonary causes, B3: cerebrovascular disease, B4: multiorgan failure,
and B5: terminal malignancy).
RESULTS: In all, 18,508 cases of UGIB were enrolled; among them, 10,428 cases from 9,375 patients
were confi rmed to have PUB, and 577 (6.2 % ) patients died. There were signifi cantly more
patients who died of non-ulcer bleeding causes (79.7 % ) than bleeding causes (18.4 % ). The
mean (s.d.) age of those who died of bleeding-related causes was higher (75.4 (12.6) years)
than that of those who died of non-bleeding causes (71.7 (13.1) years) ( P = 0.010). Most
bleeding-related deaths occurred when immediate control of bleeding failed (29.2 % ) or when
patients died within 48 h after endoscopic therapy (25.5 % ). Among those who died of
non-bleeding-related causes, multiorgan failure (23.9 % ), pulmonary conditions (23.5 % ), and
terminal malignancy (33.7 % ) were most common.
CONCLUSIONS: The majority of PUB patients died of non-bleeding-related causes. Optimization of management
should aim at reducing the risk of multiorgan failure and cardiopulmonary death instead of
focusing merely on successful hemostasis.
Am J Gastroenterol 2010; 105:84–89; doi:10.1038/ajg.2009.507; published online 15 September 2009
1 Institute of Digestive Disease, The Chinese University of Hong Kong , Shatin , NT , Hong Kong . Correspondence: Joseph J.Y. Sung, MD, PhD, FRCP , Department of
Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital , Shatin , NT , Hong Kong . E-mail: joesung@cuhk.edu.hk
Received 12 January 2009; accepted 23 April 2009
see related editorial on page 90
© 2010 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
85
STOMACH
Causes of Mortality in Patients With PUB
Most studies in PUB intervention use recurrent bleeding,
repeated endoscopic therapy, surgery, and blood transfusion
as the outcome parameter. Yet very few have shown improve-
ment in the survival of patients despite a reduction in the recur-
rent bleeding rate.  ere seems to be a discrepant outcome in
endoscopic end points vs. clinical end points. As the ultimate
aim of treatment of gastrointestinal bleeding is to save lives, it is
important to elucidate the causes of death in these patients. We
conducted this study to investigate the cause of death in PUB
patients in a large cohort from a tertiary referral center.
METHODS
e Prince of Wales Hospital, a teaching hospital for the Chinese
University of Hong Kong, serves a population of 1.2 million
people in the northeastern territory of the Hong Kong SAR.
An upper gastrointestinal bleeding (UGIB) registry was estab-
lished to collect demographic information, characteristics of
bleeding pathologies, and pharmacological, endoscopic, or
surgical treatments for peptic ulcer patients with hematem-
esis or melena since 1993. Findings at index endoscopy on
admission and at the endoscopic therapy of each patient were
recorded by endoscopists. Follow-up hemostatic procedures
were documented if patients required second endoscopy for
rebleeding ulcer within the same admission. Patients admit-
ted for PUB or those who developed bleeding a er admis-
sion for other medical conditions were prospectively collected
between 1993 and 2005. In this study, we focus on PUB. Data
extracted from the UGIB registry included ulcer location, stig-
mata of recent hemorrhage (according to the Forrest classi -
cation), nature and number of comorbid illness, Helicobacter
pylori infection, as well as the use of H
2 receptor antagonists or
PPIs, NSAIDs (including conventional NSAID and cyclooxy-
genase 2-speci c inhibitors), or antiplatelet agents (includ-
ing aspirin and clopidogrel). Presentation of hemodynamic
status, requirement of endoscopic treatment, and occurrence
of rebleeding was recorded. All clinical details were based on
the initial records of admission.
Mortality within 30 days (30-day mortality) a er index bleed-
ing is the primary outcome of this study.  ese are counted as
any causes of death within 30 days a er index bleeding, includ-
ing patients who died while still in hospital or those who had
been discharged from hospital. A er discharge from hospital,
patients with PUB were scheduled for follow-up in the ulcer
clinic at 4 6 weeks. Mortality cases within 30 days a er dis-
charge were identi ed by (i) those who were subsequently read-
mitted to hospital and died or (ii) by calling patients at home
for failing to turn up at follow-up visits. In-hospital mortality
is de ned as all cases of death during the period of hospital
stay irrespective of the duration of hospitalization.  erefore,
this included those patients who died 30 days a er admission.
Although the majority of cases were admitted for symptoms
of UGIB, there were also cases that were admitted for other
medical conditions but developed UGIB during the course of
hospital stay.
Comorbidity data were based on (i) detailed clinical his-
tory on admission, (ii) electronic patient record in the hospital
database, and (iii) structured questionnaire a er endoscopy. It
was presented as a simple dichotomous question by dedicated
research sta of the Endoscopy Center. All data were entered
prospectively.  e de nitions of serious comorbid illness
included decompensated cardiac, pulmonary, hepatic, neuro-
logical and renal disease, and advanced malignancy.
Causes of mortality were classi ed into (A) bleeding-related
death and (B) non-bleeding-related death. Under the category
of bleeding-related death, cases were further subcategorized
into (A1) uncontrolled bleeding, (A2) within 48 h a er endo-
scopy, (A3) during surgery for uncontrolled bleeding, (A4) sur-
gical complications or within 1 month a er surgery, and (A5)
endoscopic-related mortality. Under non-bleeding-related
death, cases were subcategorized into (B1) cardiac causes, (B2)
pulmonary causes, (B3) cerebrovascular disease, (B4) multi-
organ failure, and (B5) terminal malignancy. Mortality was
registered in the system in Hospital Authority. Causes of death
were independently determined by two clinicians (T.K.W.M.
and P.W.Y.C.) on the basis of clinical records in UGIB registry
and the death certi cates. When discrepancies were found, a
consensus agreement would be made with the third investigator
(J.J.Y.S.) by retrieving the complete hospital record for review.
Univariate analyses were carried out using SPSS (version
13.0; SPSS, Chicago, IL). Di erences in categorical variables
were evaluated using Pearson s 2 test or Fisher s exact test when
appropriate. Di erences in continuous variables were evaluated
using Student ’ s t -test for independent samples, a er verifying
homogeneity of variance with Levene s test.  e bleeding-related
mortalities each year were plotted against time and 2 test for
trend was carried out to detect if there is a consistent inclin-
ing or declining trend. Any missing record was excluded dur-
ing the statistical calculation. Subgroup analyses were carried
out for the patients admitted for gastrointestinal bleeding. All
tests were performed two-sided and considered to be statisti-
cally signi cant for P value < 0.05. Logistic regression was used
to estimate the odds ratio (OR) and the 95 % con dence inter-
val (CI) of various possible risk factors for the bleeding-related
mortality. Risk factors with a P value of < 0.10 in univariate
analyses were included in a multiple logistic regression model
and analyzed using the backward approach.  e 95 % CI of
the OR was used for assessing the statistical signi cance at the
conventional level of 0.05.
RESULTS
Between 1993 and 2005, a total of 18,508 UGIB episodes were
entered into the GIB registry. Among them, a total of 10,428
cases from 9,375 patients were con rmed to have PUB.  is
included 612 (6.5 % ) patients who died during hospital stay or
within 30 days a er index endoscopy, 8,667 (92.5 % ) patients
who survived the bleeding episode(s), and 96 (1 % ) dis-
charged patients who died a er 30 days of index endoscopy.
A total of 577 (6.2 % ) patients died within 30 days a er index
The American Journal of GASTROENTEROLOGY VOLUME 105 | JANUARY 2010 www.amjgastro.com
86
STOMACH
Sung et al.
endoscopy.  e characteristics of patients were compared
between those who survived and those who died within 30
days a er endoscopy ( Table 1 ). e surviving patients were
younger (61.0 vs. 72.5 years), with less severe comorbid illness.
ey were more likely to have a previous history of ulcer and
H. pylori infection, and less likely to be users of H
2 blocker / PPI
and NSAID / aspirin. ey were more likely to be admitted just
for UGIB and were found to have clean-based ulcer. Patients
with hemodynamic shock and clinical rebleeding were more
likely to die within 40 days a er index bleeding.
Out of 577 mortality cases within 30 days, 106 (18.4 % )
patients were classi ed as bleeding-related mortality and 460
(79.7 % ) as non-bleeding-related mortality ( Tabl e 2 ). Causes
of 30-day mortality in 11 (1.9 % ) patients were unclassi-
ed because of insu cient clinical information availability
( Tabl e 2 ). A unanimous decision on the cause of death was
reached in 551 (95.5 % ) cases in the  rst round. Consen-
sus diagnoses reached a er clinical notes review and a third
clinician s input were given in 4.5 % .
e mean (s.d.) age of 106 patients who died of bleeding-
related mortality within 30 days was 75.4 (12.6) years, of which
60.4 % were males. Among these patients, uncontrolled or
recurrent bleeding from peptic ulcer was reported in 29.2 % ,
and death from circulatory failure within 48 h a er endoscopy
was reported in 25.5 % . Surgical or endoscopic complications
accounted for 29.2 and 13.2 % , respectively, of cases of 30-day
mortality. Only 2.8 % of subjects died as a result of uncontrolled
bleeding during surgery ( Ta ble 2 ).
e mean (s.d.) age of 460 patients who died of non-bleeding-
related causes was 71.7 (13.1) years, of which 65.9 % were males.
Among these patients, the most common causes of death were
terminal malignancy (33.7 % ), multiorgan failure (23.9 % ), and
pulmonary disease (23.5 % ). Cardiac diseases (including acute
coronary syndrome and heart failure) and cerebrovascular
diseases constituted 13.5 and 5.4 % , respectively. As a whole
group, 435 of 577 (75.4 % ) of 30-day mortality cases were due to
terminal malignancy, multiorgan failure, and cardiopulmonary
decompensation.
A total of 469 (4.5 % ) patients died during the period of
hospital stay a er the index bleeding. Among these patients,
104 (22 % ) died of bleeding-related causes, 358 (77 % ) died of
non-bleeding-related causes, and 7 (1 % ) were unclassi ed.
Overall, 50.0 % in the bleeding-related group were attributed
to uncontrolled bleeding (24.0 % ) or circulatory failure with
48 h a er endoscopy (26.0 % ), and 80.7 % in the non-bleeding-
related group were attributed to terminal malignancy (23.7 % ),
multiorgan failure (29.6 % ), and pulmonary diseases (27.4 % ).
Patients who had PUB before admission and those who
developed PUB a er admission are listed separately in Tabl e 3 .
Patients who had PUB before admission were older and were
more likely to have a history of peptic ulcers and a di erent
distribution of peptic ulcers.
Univariate analysis showed that patients who died of bleed-
ing-related causes were older than those who died of non-
bleeding-related causes ( P = 0.010) ( Tabl e 4 ). ose who had
a history of peptic ulcer disease were also more likely to die
from bleeding than those who had no ulcer history (31.1 vs.
18.5 % , P = 0.005). e use of NSAID or aspirin is signi cantly
more common in the bleeding-related death group than in
the non-bleeding death group (86.4 vs. 63.2 % , P = 0.003). e
anatomical locations of peptic ulcers (i.e., gastric, duodenal,
or anastomotic ulcer) had no bearing on the cause of death.
On the other hand, patients admitted with hemodynamic
shock (39.4 vs. 22.4 % , P < 0.001) and those with actively bleed-
ing ulcers on index endoscopy (42.5 vs. 22.4 % , P < 0.001)
were associated with a higher risk of bleeding-related death.  e
Table 1 . Characteristics of patients who survived or died from
peptic ulcer bleeding
Surviving
patients
( n =8,667)
Patients died
within 30 days
after endo scopy
( n =577) P value
Mean age, years (s.d.) 61.0 (18.4) 72.5 (13.1) < 0.001
Male ( % ) 5,715 (65.9) 372 (64.5) 0.471
Patients with ulcer
history ( % )
3,053 (35.3) 118 (20.6) < 0.001
Ulcer location ( % )
Gastric ulcer 3,204 (37.0) 245 (42.5)
Duodenal ulcer 4,579 (52.8) 242 (41.9)
Both 655 (7.6) 63 (10.9)
Anastomotic ulcer 227 (2.6) 27 (4.7) < 0.001
Severe comorbid illness ( % )
0 5,861 (67.6) 123 (21.3)
1 2,106 (24.3) 287 (49.7)
2 624 (7.2)
139 (24.1)
3 76 (0.9) 28 (4.9) < 0.001
Use of H
2 blocker
or PPI ( % )
654 (7.9) 66 (12.2) < 0.001
Use of NSAID or
aspirin ( % )
1385 (48.7) 184 (67.4) < 0.001
Helicobacter pylori
infection ( % )
3,521 (61.0) 65 (23.0) < 0.001
Type of ulcer ( % )
Active bleeding ulcer 1,362 (17.1) 149 (25.8)
Clot or vessel at base
of ulcer
2,323 (29.1) 211 (36.6)
Clean-based ulcer 4,301 (53.9) 217 (37.6) < 0.001
Hemodynamic shock
( % )
718 (8.4) 144 (25.2) < 0.001
Admitted for UGIB ( % ) 7,888 (91.0) 334 (58.0) < 0.001
Clinical rebleeding ( % ) 233 (8.8) 73 (27.8) < 0.001
NSAID, nonsteroidal anti-infl ammatory drug; PPI, proton pump inhibitor; UGIB,
upper gastrointestinal bleeding.
© 2010 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
87
STOMACH
Causes of Mortality in Patients With PUB
percentage of patients admitted for UGIB, patients with clinical
evidence of recurrent bleeding, and patients requiring repeated
endoscopic therapy were not signi cantly di erent between
the two groups of 30-day mortality cases ( Tab le 4 ). In non-
bleeding-related mortality, a signi cantly higher proportion
of patients with severe comorbid illnesses have been reported
(63.2 vs. 82.6 % , P < 0.001). H. pylori infection of the two groups
showed no signi cant di erence ( Tab le 4 ). Using a multivariate
logistic regression model, use of NSAID or aspirin, as well as
the endoscopic appearance of ulcer and hemodynamic shock,
was found to be an independent variable predicting bleeding-
related death ( Tabl e 5 ).
Overall, 50.0 % of patients in the bleeding-related mortality
group and 28.9 % patients in the non-bleeding-related mor-
tality group died within 3 days of index bleeding ( P < 0.001).
Morta lity related to bleeding over the period 1993 2005 ranges
from 13.3 to 39.4 % ( Figure 1 ). ere is no signi cant trend
shown on the bleeding-related mortality in the study period
( P = 0.087).
DISCUSSION
Mortality remains high in patients presenting with PUB and
this study shows that around 80 % of them died of non-bleed-
ing-related causes. In this prospective cohort study enrolling
over 10,000 cases of PUB, terminal malignancy, multiorgan
failure, and cardiopulmonary decompensation were the most
important causes of death, accounting for 75 % of cases.
e ndings from this study are strengthened by the fact that
in this single referral center a dedicated team of medical and
surgical experts provided service to PUB patients.  e protocol
of management has not been signi cantly changed in the last 15
Table 2 . Causes of death of 577 patients who died within
30 days after index bleeding
Mortality cases
n =577 Subcategories n Percentage
Bleeding related
n =106 (18.4 % )
Uncontrolled bleeding /
rebleeding
31 29.2
Within 48 h after endo-
scopy without other cause
27 25.5
During surgery for
uncontrolled bleeding
3 2.8
Surgical complications or
within 1 month after sur-
gery without other cause
31 29.2
Endoscopy-related
complication
14 13.2
Non bleeding
related n =460
(79.7 % )
Cardiac diseases
(e.g., ACS, heart failure)
62 13.5
Pulmonary diseases
(e.g., COPD, pneumonia)
108 23.5
Multiorgan failure 110 23.9
Neurological diseases
(e.g., stroke)
25 5.4
Terminal malignancy 155 33.7
Unclassifi ed
n
=11 (1.9 % )
ACS, acute coronary syndrome; COPD, chronic obstructive pulmonary disease.
Table 3 . Comparison of patients with PUB as a presenting
symptom before admission or after patients were admitted for
other reasons (excluding 11 cases with unclassifi ed cause of
death)
PUB before
admission
( n =329)
PUB after
admission
( n =237) P value
Mean age, years (s.d.) 73.5 (12.7) 70.9 (13.6) 0.021
Male ( % ) 208 (63.2) 159 (67.1) 0.342
Patients with ulcer
history ( % )
80 (24.5) 37 (15.7) 0.011
Ulcer location ( % )
Gastric ulcer 148 (45.0) 92 (39.0)
Duodenal ulcer 122 (37.1) 115 (48.3)
Both 43 (13.1) 20 (8.5)
Anastomotic ulcer 16 (4.9) 10 (4.2) 0.040
Severe comorbid illness ( % )
0 80 (24.3) 39 (16.5)
1 161 (48.9) 120 (50.8)
2 73 (22.2) 65 (27.5)
3 15 (4.6) 13 (5.5) 0.116
Use of H
2 blocker or
PPI ( % )
35 (11.5) 31 (13.8) 0.436
Use of NSAID or aspirin
( % )
106 (68.4) 73 (65.2) 0.582
Helicobacter pylori
infection ( % )
38 (23.8) 26 (22.6) 0.825
Type of ulcer ( % )
Active bleeding ulcer 90 (27.4) 58 (24.6)
Clot or vessel at base
of ulcer
125 (38.0) 83 (35.2)
Clean-based ulcer 114 (34.7) 96 (40.5) 0.360
Hemodynamic shock ( % ) 80 (24.5) 63 (27.0) 0.491
Clinical rebleeding ( % ) 31 (21.5) 27 (27.8) 0.261
Required endoscopic
re-treatment ( % )
23 (16.0) 22 (22.7) 0.190
Bleeding-related
mortality ( % )
65 (19.8) 41 (17.3) 0.460
NSAID, nonsteroidal anti-infl ammatory drug; PPI, proton pump inhibitor; PUB,
peptic ulcer bleeding.
The American Journal of GASTROENTEROLOGY VOLUME 105 | JANUARY 2010 www.amjgastro.com
88
STOMACH
Sung et al.
using a heater probe. Hemoclips were used but only in < 5 %
of the cases. In the last 8 years, intravenous high-dose PPIs
(including omeprazole, pantoprazole, and esomeprazole) had
been added as an adjuvant to endoscopic therapy. A er endo-
scopic therapy, patients were nursed in a closely monitored
gastrointestinal bed in the combined unit. Oral feeding was
resumed on the next day or as soon as the patients condition
became stable. Intravenous PPIs were maintained for 3 days
and replaced by oral medications including anti-helicobacter
therapy, if deemed appropriate. Indications for surgery had
remained unchanged, i.e., for uncontrolled bleeding in index
endoscopy or recurrent bleeding not responding to endoscopic
therapy. Patients would be nursed in the intensive care unit if
they required, or if they were likely to require ventilatory sup-
port or cardiac resuscitation. Variations in management proto-
col, suboptimal endoscopic or medical therapy, and decisions
on surgery or intensive care unit would not confound the  nd-
ings in this study.
e implications of this  nding are self-evident. If morta lity
among PUB cases is not necessarily related to uncontrolled
bleeding, it is very hard to improve on it through advance-
ment in treatment targeting on bleeding control alone.  e
rebleeding rates from major studies in PUB, using a combina-
tion of endoscopic hemostasis and adjuvant acid-suppressing
therapy, have been shown to be reduced to 5 8 % (13,14) and it
years. Endoscopy has always been the  rst line of investigation
and treatment of PUB and has been o ered within 24 h a er
admission. Endoscopic hemostasis has always been a combina-
tion of epinephrine injection followed by thermal coagulation
Table 4 . Univariate analysis between bleeding and non-
bleeding-related mortality (excluding 11 cases with
unclassifi ed cause of death)
Bleeding
related mortality
( n =106)
Non-bleeding-
related mortality
( n =460) P value
Mean age (s.d.) 75.4 (12.6) 71.7 (13.1) 0.010
Male ( % ) 64 (60.4) 303 (65.9) 0.286
Patients with ulcer
history ( % )
32 (31.1) 85 (18.5) 0.005
Ulcer location ( % )
Gastric ulcer 35 (33.0) 205 (44.6)
Duodenal ulcer 54 (50.9) 183 (39.8)
Both 11 (10.4) 52 (11.3)
Anastomotic
ulcer
6 (5.7) 20 (4.3) 0.129
Severe comorbid illness ( % )
0 39 (36.8) 80 (17.4)
1 40 (37.7) 241 (52.4)
2 21 (19.8) 117 (25.4)
3 6 (5.7) 22 (4.8)
< 0.001
Use of acid sup-
pressing agents ( % )
11 (11.3) 55 (12.7) 0.713
Use of NSAID or
aspirin ( % )
38 (86.4) 141 (63.2) 0.003
Helicobacter pylori
infection ( % )
15 (31.9) 49 (21.5) 0.124
Endoscopic appearance of ulcer ( % )
Active bleeding
ulcer
45 (42.5) 103 (22.4)
Clot or vessel at
base of ulcer
46 (43.4) 162 (35.2)
Clean-based
ulcer
15 (14.2) 195 (42.4) < 0.001
Hemodynamic
shock ( % )
41 (39.4) 102 (22.4) < 0.001
Admitted for UGIB
( % )
65 (61.3) 264 (57.5) 0.474
Clinical rebleeding
( % )
16 (27.6) 42 (23.0) 0.472
Required endo-
scopic re-treatment
( % )
14 (24.1) 31 (16.9)
0.220
NSAID, nonsteroidal anti-infl ammatory drug; UGIB, upper gastrointestinal
bleeding.
Table 5 . Multivariate analysis between bleeding and
non-bleeding-related mortality (excluding 11 cases with
unclassifi ed cause of death)
OR 95 % CI
Use of NSAID or aspirin 3.70 1.43 9.60
Endoscopic appearance of ulcer
Active bleeding ulcer 12.96 2.82 59.55
Clot or vessel at base of ulcer 12.29 2.75 54.95
Hemodynamic shock 3.75 1.77 7.96
CI, confi dence interval; NSAID, nonsteroidal anti-infl ammatory drug; OR, odds ratio.
Bleeding mortality
Non-bleeding
mortality
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005
Year
Deaths (%)
Figure 1 . Incidences of bleeding-related and non-bleeding-related
mortality between the years 1993 2005.
© 2010 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY
89
STOMACH
Causes of Mortality in Patients With PUB
would be very di cult, if not impossible, to reduce this further
to approach zero. As the majority of patients with PUB these
days are of advanced age, users of NSAID and aspirin, impli-
cated with multiple comorbid illnesses, the endeavor to further
reduce this rebleeding rate is an uphill battle. Energy should be
directed to improve on supportive care or prevent complica-
tions of the other organ systems instead of focusing merely on
the gastrointestinal tract.
It is common practice to withhold aspirin or clopidogrel for a
period of time a er PUB. Discontinuation of antiplatelet agents
may have increased the risk of non-bleeding-related deaths as
patients with cardiovascular and cerebrovascular diseases were
exposed to unprotected vascular complications. In our earlier
study comparing the early resumption of aspirin vs. withholding
for 8 weeks a er PUB, there was a signi cantly increased mortality
in the latter group (15) .  e risk and bene t of early resumption
of antiplatelet agents deserve further evaluation. Future studies
should look at the management of PUB patient as a whole instead
of focusing only on gastrointestinal bleeding. On the other hand,
gastrointestinal bleeding can be seen as a terminal event in some
patients who are dying from other conditions such as metastatic
cancers and multiorgan failure. It would be very hard to make any
substantial improvement in their clinical outcome.
ere are several limitations in this study. First, as a single
center, the generalizability of this  nding is a concern. However,
the prospective collection of these data through a well-organ-
ized GIB registry guarantees good quality of information for
analysis.  e high volume of PUB cases seen by this center also
strengthens the  ndings in this study. In multicenter studies
or studies using retrospective data, the variable quality of data
may impose di culties in interpretation. Second, the deci-
sion of cause of death may not be strictly forward.  ere were
cases with evidence on the cause of death pointing in di erent
directions and, indeed, in some cases, more than one possible
cause of death was possible. To minimize bias, two experienced
clinicians made their diagnosis independently and a third clini-
cian s opinion was added in an attempt to reach a consensus.  e
unanimous diagnosis reached by 95 % in the  rst round suggests
that a majority of the cases were undisputed.
In conclusion, a majority of patients with PUB in hospital died
of non-bleeding-related causes.  is nding calls for a stronger
support of other major organ systems in these patients. Future
studies should be directed to explore ways to improve the over-
all outcome of the patients.
CONFLICT OF INTEREST
Guarantor of the article: Joseph J.Y. Sung, MD, PhD, FRCP.
Speci c author contributions: Study design and writing of
the paper: Joseph J.Y. Sung; result analysis: Kelvin K.F. Tsoi;
data collection: Terry K.W. Ma and Man-Yee Yung; and data
collection and writing of the paper: James Y.W. Lau and
Philips W.Y. Chiu.
Financial support: None.
Potential competing interests: Joseph J.Y. Sung is on the
advisory board of AstraZeneca and is a speaker for Astra-
Zeneca and Nycomed. James Y.W. Lau is on the advisory
boards of and is a speaker for AstraZeneca and Nycomed.
Study Highlights
WHAT IS CURRENT KNOWLEDGE
3 Peptic ulcer bleeding has a mortality rate of 5 10 % .
3 Acid-suppressing agents, endoscopic hemostasis, and
surgery are effective in bleeding control.
3 There is little improvement in survival rate despite these
advances in treatment.
WHAT IS NEW HERE
3 Overall, 80 % of mortality is not related to bleeding.
3 Multiorgan failure, cardiopulmonary conditions, and
terminal malignancy constitute the most common
causes in these patients.
3 Over 50 % of bleeding-related mortality occurred within
3 days after onset of bleeding.
REFERENCES
1 . L a s s e n A , H a l l a s J , S c h a alitzky de Muckadell OB . Complicated and
uncomplicated peptic ulcers in a Danish county 1993 2002: a population-
based cohort study . Am J Gastroenterol 2006 ; 101 : 945 – 53 .
2 . L e w i s J D , B i l k e r W B , B r e n s i n g e r C et al. Hospitalization and mortality rates
from peptic ulcer disease and GI bleeding in the 1990s: relationship to sales
of nonsteroidal anti-in ammatory drugs and acid suppression medications .
Am J Gastroenterol 2002 ; 97 : 2540 – 9 .
3 . R a m s o e k h D , v a n L e e r d a m M E , R a u w s E A et al. Outcome of peptic ulcer
bleeding, nonsteroidal anti-in ammatory drug use, and Helicobacter pylori
infection . Clin Gastroenterol Hepatol 2005 ; 3 : 859 – 64 .
4 . C o o p e r G S , Y u a n Z , R o s e n t h a l G E et al. Lack of gender and racial di er-
ences in surgery and mortality in hospitalized medicare bene ciaries with
bleeding peptic ulcer . J Gen Intern Med 1997 ; 12 : 485 – 90 .
5 . K u b b a A K , C h o u d a r i C , R a j g o p a l C et al. Reduced long-term survival fol-
lowing major peptic ulcer haemorrhage . Br J Surg 1997 ; 84 : 265 – 8 .
6 . H a s s e l g r e n G , C a r l s s o n J , L i n d T et al. Risk factors for rebleeding and fatal
outcome in elderly patients with acute peptic ulcer bleeding . Eur J Gastro-
enterol Hepatol 1998 ; 10 : 667 – 72 .
7 . Bini EJ , Cohen J . Endoscopic treatment compared with medical therapy
for the prevention of recurrent ulcer hemorrhage in patients with adherent
clots . Gastrointest Endosc 2003 ; 58 : 707 – 14 .
8 . C h i u P W Y , L a m C Y , L e e S W et al. E ect of scheduled second therapeutic
endoscopy on peptic ulcer rebleeding: a prospective randomized trial .
Gut 2003 ; 52 : 1403 – 7 .
9 . M o s e H , L a r s e n M , R i i s A et al. irty-day mortality a er peptic ulcer
bleeding in hospitalized patients receiving low-dose aspirin at time of
admission . Am J Geriatr Pharmacother 2006 ; 4 : 244 – 50 .
1 0 . o m s e n R W , R i i s A , C h r i s t e n s e n S et al. Diabetes and 30-day mortality
from peptic ulcer bleeding and perforation . Diabetes Care 2006 ; 29 : 805 – 10 .
11 . Rockall TA , Logan RF , Devlin HB et al. Incidence of and mortality from
acute upper gastrointestinal haemorrhage in the United Kingdom. Steering
Committee and members of the National Audit of Acute Upper Gastro-
intestinal Haemorrhage . BMJ 1995 ; 311 : 222 – 6 .
1 2 . O h m a n n C , I m h o f M , R u p p e r t C et al. Time-trends in the epidemiology of
peptic ulcer bleeding . Scand J Gastroenterol 2005 ; 40 : 914 – 20 .
1 3 . L a u J Y , S u n g J J , L e e K K et al. E ect of intravenous omeprazole on
recurrent bleeding a er endoscopic treatment of bleeding peptic ulcers .
N Engl J Med 2000 ; 343 : 310 – 6 .
1 4 . S u n g J J , T s o i K K , L a i L H et al. Endoscopic clipping vs. injection and
thermo-coagulation in the treatment of bleeding non-variceal upper
gastrointestinal bleeding: a meta-analysis . Gut 2007 ; 56 : 1364 – 72 .
1 5 . S u n g J J , L a u J Y , C h i n g J Y et al. Can aspirin be reintroduced with proton
pump inhibitor infusion a er endoscopic hemostasis? A double blinded
randomized controlled trial . Gastroenterology 2006 ; 130 (Suppl 2) : A44 .
... It has been shown that despite medical advances in both diagnostic and therapeutic approach of patients with AUGIB, mortality remained stable over the years around 5-10%. Also, the majority of deaths are not related directly to the bleeding event itself, but rather to coexisting diseases, especially cardiovascular [11]. ...
... Overall mortality rates in our patients were similar in both periods in our area. It is known that the majority of deaths in patients with AUGIB are not related to exsanguination but rather to coexisting diseases, especially cardiovascular due to inability of these patients to recover from rebleeding or surgery [11]. A recent meta-analysis reported UGIB secondary to peptic ulcer bleeding patients with comorbidities were at severalfold higher risk of overall mortality when compared to patients without comorbidities [34]. ...
Article
Full-text available
Background: Acute upper gastrointestinal bleeding (AUGIB) remains a common medical emergency with considerable morbidity and mortality. The aim of this study was to describe the patient characteristics, diagnoses and clinical outcomes of patients presenting with AUGIB nowadays and compare these with those of patients 15 years ago. Methods: This was a single-center survey of adults (> 16 years) presenting with AUGIB to a tertiary hospital. Data from 401 patients presenting with AUGIB in a tertiary hospital between January 1, 2019 and December 31, 2020 were analyzed and compared with data from 434 patients presenting with AUGIB at the same hospital between January 1, 2004 and December 31, 2005. Results: Nowadays, patients were older, mean age was 69.5 (± 15.4) vs. 66.2 (± 16.0) years, they had more frequently coexisting diseases (83.5% vs. 72.8%), especially cardiovascular diseases (62.3% vs. 52.5%), and more individuals were inpatients at onset of bleeding (8.2% vs. 4.1%). In addition, more patients were under anticoagulants (18.5% vs. 6.2%), but less were under acetylsalicylic acid ± clopidogrel (36.9% vs. 33.9%). Carlson Comorbidity Index was higher nowadays (5.6 ± 6.4 vs. 3.4 ± 2.3). Moreover, a peptic ulcer was less frequently found as the cause of bleeding (38.4% vs. 56.9%), while more often nowadays endoscopy was negative (12.7% vs. 3.5%). In patients with peptic ulcer, active bleeding on endoscopy was less frequent (7.1% vs. 14.2%). Also, bleeding spots requiring hemostasis were less common on endoscopy (39.6% vs. 49.4%) and more patients were without spots of recent bleeding (49.4% vs. 38.9%). Finally, the rate of rebleeding statistically decreased (7.8% vs. 4.2%), while overall mortality remained relatively unchanged (5.0% vs. 6.2%). Conclusions: AUGIB episodes nowadays are less severe with less peptic ulcer bleeding, but the patients are older and with more comorbidities.
... patients. The median CHAMPS score, GBS, cRS, AIMS65 score, and ABC score for each eligible patient was 1 (0-2), 5.5 (2-9), 3 (2-4), 1 (1)(2), and 2 (1-5), respectively. ROCs comparing the performance of these 5 scoring systems in predicting in-hospital mortality are shown in Fig. 3. ...
... LGIB with an onset during hospitalization is known to be associated with higher mortality in comparison to outpatient-onset LGIB 2,18,19 . In any case, the present study was consistent with previous studies dealing with UGIB or LGIB patients 1,2,15,20 , in that it demonstrated that uncontrolled bleeding accounted for the cause of death in a small portion (10%) of the cases in which patients died after LGIB, with bleeding-unrelated causes accounting for the vast majority (90%) of the remaining deaths. This finding reinforces the importance of general intensive management for patients with GIB to improve their overall prognosis, irrespective of the source of bleeding (UGIB or LGIB), without merely focusing on the local control of bleeding. ...
Article
Full-text available
We have recently developed a simple prediction score, the CHAMPS score, to predict in-hospital mortality in patients with upper gastrointestinal bleeding. In this study, the primary outcome of this study was the usefulness of the CHAMPS score for predicting in-hospital mortality with lower gastrointestinal bleeding (LGIB). Consecutive adult patients who were hospitalized with LGIB at two tertiary academic medical centers from 2015 to 2020 were retrospectively enrolled. The performance for predicting outcomes with CHAMPS score was assessed by a receiver operating characteristic curve analysis, and compared with four existing scores. In 387 patients enrolled in this study, 39 (10.1%) of whom died during the hospitalization. The CHAMPS score showed good performance in predicting in-hospital mortality in LGIB patients with an AUC (95% confidence interval) of 0.80 (0.73–0.87), which was significantly higher in comparison to the existing scores. The risk of in-hospital mortality as predicted by the CHAMPS score was shown: low risk (score ≤ 1), 1.8%; intermediate risk (score 2 or 3), 15.8%; and high risk (score ≥ 4), 37.1%. The CHAMPS score is useful for predicting in-hospital mortality in patients with LGIB.
... And GU belongs to the gastric abscess and stuffiness of the stomach in traditional Chinese medical science (TCM). The incidence of GU is 20-60 cases per 100,000 people with 5%-10% of mortality worldwide [3]. Some studies have indicated that patients with long-term GU have a higher risk of the occurrence of gastric cancer. ...
Article
Full-text available
Objective: To research the mechanism of action and transcriptomic characteristics for the intervention effect of self-made Chaihuang decoction (Sichs) on gastric ulcer (GU) rats with liver qi stagnation and spleen deficiency and to clarify the therapeutic pathway and effective target. Methods: Thirty SD rats were randomly divided into the control group, model group, and Sichs group (10 rats per group). The model of GU rats with liver qi stagnation and spleen deficiency was established through multifactor compound simulation of traditional Chinese medical (TCM) etiology and acetic acid method. Histopathological changes in the gastric antrum tissue were observed with H&E staining. RNA sequencing (RNA-seq) was utilized to check differentially expressed genes (DEGs) in the gastric antrum tissues of rats, and gene ontology (GO) and KEGG pathway enrichment analyses were performed. The key DEGs were validated using qRT-PCR. Results: Sichs could ameliorate gastric antrum tissue injury in GU rats with liver qi stagnation and spleen deficiency. After RNA-seq, it was found that Sichs could reverse 225 upregulated genes and 26 downregulated genes in the model group. And the DEGs between the Sichs group and the model group were related to cell division, complement activation, and phospholipase A2 (Pla2g2a) activity. According to KEGG pathway analysis, DEGs between the two groups were mainly enriched in signaling pathways such as cell cycle, p53 signaling pathway, and linolenic acid metabolism. The validation results of the four key DEGs were consistent with the analysis trend of sequencing results. Conclusion: Sichs can effectively improve GU with liver qi stagnation and spleen deficiency in rats through the signaling pathways related to cell cycle and lipid metabolism.
... As one of the most common diseases of the digestive system worldwide, gastric ulcer (GU) can be triggered by a variety of factors, including unhealthy eating habits, helicobacter pylori infection, excessive alcohol consumption, use of nonsteroidal anti-inflammatory drugs (NSAIDs) and destruction of the gastric mucosal protective barrier [1,2]. Stress gastric ulcer is an acute haemorrhagic injury characterised by ulceration of the gastric mucosa caused by environmental stress, the decline in the mucosal prostaglandin and mucoprotein, an increase in oxidative stress and neutrophil activation and the suppression of the gastric mucosal cell proliferation [3,4]. ...
Article
Full-text available
Sarcodon aspratus is a popular edible fungus for its tasty flavour and can be used as a dietary supplement for its functional substances. This study was conducted to evaluate the potential health benefits of Sarcodon aspratus polysaccharides (SAFP) on water immersion and restraint stress (WIRS)-induced gastric ulcer in rats. The results indicated that SAFP could decrease myeloperoxidase (MPO) activity and plasma corticosterone levels, as well as enhance Prostaglandin E2 (PGE2) and Nitrate/nitrite (NOx) concentration in rats. Furthermore, SAFP significantly attenuated the stress damage, inflammation, pathological changes and gastric mucosal lesion in rats. Moreover, high-throughput pyrosequencing of 16S rRNA suggested that SAFP modulated the dysbiosis of gut microbiota by enhancing the relative abundance of probiotics, decreasing WIRS-triggered bacteria proliferation. In summary, these results provided the evidence that SAFP exerted a beneficial effect on a WIRS-induced gastric ulcer via blocking the TLR4 signaling pathway and activating the Nrf2 signaling pathway. Notably, SAFP could modulate the WIRS-induced dysbiosis of gut microbiota. Thus, SAFP might be explored as a natural gastric mucosal protective agent in the prevention of gastric ulcers and other related diseases in the food and pharmaceutical industries.
... 35,36 Risk factors for mortality other than elderly age include high ASA grade, delayed operative management, size of perforation and multi-organ failure. 37,38 These risk factors were not analysed in this review due to lack of data in the included studies. Moreover, leak is considered a significant risk factor for mortality which reported as high as 50% in patients developed leak after repair of the perforation. ...
Article
Aims To evaluate comparative outcomes of laparoscopic repair of perforated peptic ulcer with omental patch versus without omental patch. Methods A systematic search of multiple electronic data sources was conducted, and all studies comparing laparoscopic repair of perforated peptic ulcer (PPU) with and without omental patch were included. Operative time, postoperative complications, re-operation and mortality were the evaluated outcome parameters for the meta-analysis. Revman 5.3 was used for data analysis. Results Four observational studies reporting a total number of 438 patients who underwent laparoscopic repair of PPU with (n = 268) or without (n = 170) omental patch were included. Operative time was significantly shorter in no-omental patch group (NOP) when compared to omental patch group ( P = .02). There was no significant difference in the risk of postoperative ileus (Odd ratio (OR) .76, P = .61), leakage (OR 1.17, P = .80), wound infection (OR 1.89, P = .34), intra-abdominal abscess (OR 1.17, P = .87), re-operation (OR .00, P = .94) and mortality (OR .55, P = .48). Moreover, length of hospital stay was comparable between the two groups ( P = .81). Conclusion Laparoscopic repair of PPU with or without omental patch have comparable postoperative complications and mortality rate. However, considering the shorter operative time, no-omental patch approach is an attractive and more favourable choice. Well-designed randomized controlled trials are needed to investigate this comparison.
... Some studies have reported a delayed diagnosis of GI cancer due to the impact of COVID-19 (3,4), but the situational change in the diagnosis of peptic ulcer disease (PUD) during COVID-19 has not been widely reported. PUD, a commonly detected condition during upper GI endoscopy, was responsible for more than 300,000 deaths globally in 2013, mostly due to GI hemorrhagic complications (5), and was associated with high mortality despite advances in endoscopic and pharmacological treatment (6,7). Early detection of PUD contributes to the prevention of GI hemorrhage and diagnosis of gastric cancer. ...
Article
Full-text available
Objectives The coronavirus disease 2019 (COVID-19) pandemic has disrupted the practice of gastrointestinal (GI) endoscopy units and may increase the risk of digestive disorders. We described the situational changes in GI endoscopy and peptic ulcer disease (PUD) proportion during COVID-19 in Vietnam and examined the associated factors. Methods A retrospective ecological study was conducted on data of Hanoi Medical University Hospital, Vietnam. The number of upper GI endoscopy and the proportion of GI emergency endoscopy and PUD were compared between 2019 and 2020 by month (January to June). Log-binomial regression was used to explore associated factors of GI emergency endoscopy and PUD. Results The number of endoscopies decreased remarkably during the nationwide social distancing in April 2020. Compared to April 2019, the proportion in April 2020 of both GI emergency endoscopy [4.1 vs. 9.8%, proportion ratio (PR) 2.39, 95% CI 2, 2.87], and PUD [13.9 vs. 15.8%; PR, 1.14; 95% CI, 1.01, 1.29] was significantly higher. In log-binomial models, the proportion of GI emergency endoscopy was higher in April 2020 compared to April 2019 (adjusted PR, 2.41; 95% CI, 2.01, 2.88). Male sex and age of ≥50 years were associated with an increased PUD and GI emergency conditions. Conclusion The proportion of both GI emergency endoscopy and PUD was significantly higher during the time of the state of emergency due to the ongoing COVID-19 pandemic in 2020 when compared to 2019 at the same health facility in Vietnam. The findings suggest that healthcare delivery reforms during the era of an emerging pandemic are required to reduce digestive disorders, in particular, and chronic diseases in general.
... They have low toxicity for enteral and parenteral administration. It has been established that the catholyte has an anabolic effect and stimulates growth processes, as well as physiological and reparative regeneration (21,22). One of the well-studied effects of anolyte is antiseptic action. ...
Article
Gastroduodenal bleeding is one of the most challenging issues in surgery nowadays. The crude mortality rate due to severe blood loss in gastrointestinal bleeding is very high. Therefore, the use of medications to prevent severe blood loss and protect cells from the harmful effects of hypoxia should be the focus of attention in these conditions. This experimental study was carried out to establish changes in blood parameters and humoral immunity in rats after intestinal anastomoses combined with acute blood loss after the application of catholyte and anolyte. The study included 45 male Wistar rats weighing 290-320 g that were divided equally (15 animals per group) into three groups of intact animals (group 1), animals exposed to the small bowel resection (1.5 cm) with the end-to-end anastomosis and simulated acute blood loss (group 2), and animals exposed to the small bowel resection with end-to-end anastomosis and simulated acute blood loss that were daily given catholyte in the postoperative period group (group 3). After the surgery, the rats were given a catholyte solution per os, and the operative wound was treated with an anolyte. The blood samples and the wall of the small intestine in the anastomotic zone were used as a biological substrate to study the effect of catholyte on changes in the body during the healing process. The experiment was conducted for 15 days, and the data were recorded in two intervals on the 5th and 15th days after starting the experiment. The analyzed materials evidenced that the use of catholyte and liquid with negative oxidoreduction potential (ORP) (minus 500-520 mV) resulted in positive changes in the blood cell count, humoral immunity, and phagocytic activity impaired after the small bowel resection and blood loss. The use of an anolyte disinfectant (liquid with positive ORP+710-770 mV) prevented bacterial contamination of the surgical wound. The obtained findings proved that the catholyte had a positive effect on humoral immunity and healing processes in the anastomotic zone. Furthermore, the anolyte prevented the development of purulent complications and inflammation in the area of the surgical wound, and therefore, promoted the healing processes.
Article
Background Sepia officinalis ink is a bioactive secondary metabolite rich in melanin granules, which has a wide range of nutritional and therapeutic values and also has been used to prevent various gastrointestinal disorders. Gastric ulcer, the most common gastrointestinal disease, is characterized by severe gastric mucosa damage, and its prevention is currently one of the main goals of clinical and experimental studies. Thus, the present study was focused on evaluating the potential gastroprotective efficacy of Sepia officinalis ink extract (SOIE) against ethanol-induced gastric ulcer in rats. Results The current results revealed that SOIE administration at the two selected doses improved significantly gastric mucosa integrity as indicated by the significant ( P < 0.05) amelioration in gastric secretion indices (pH and volume) and the marked decrease in the ulcer index. Moreover, SOIE could counteract the gastric oxidative stress induced by ethanol via a marked decline in malondialdehyde content as well as a significant ( P < 0.05) increment in glutathione content and antioxidant enzymes activities (catalase and glutathione-s-transferase). Additionally, SOIE treatment caused a significant ( P < 0.05) reduction in gastric nitric oxide content. Respecting morphological and histopathological studies, SOIE treatment at 200 mg/kg body weight caused marked healing of gastric lesions as indicated by no hemorrhagic bands or injuries observed as well as significantly reduced severity score of ulcer. Conclusions SOIE could be used as a promising alternative antiulcerogenic compound to treat severe gastric lesions.
Article
Full-text available
To describe the current epidemiology of acute upper gastrointestinal haemorrhage. Population based, unselected, multicentre, prospective survey. 74 hospitals receiving emergency admissions in four health regions in the United Kingdom. 4185 cases of acute upper gastrointestinal haemorrhage in which patients were aged over 16 years identified over four months. Incidence and mortality. The overall incidence of acute upper gastrointestinal haemorrhage in the United Kingdom is 103/100,000 adults per year. The incidence rises from 23 in those aged under 30 to 485 in those aged over 75. At all ages incidence in men was more than double that in women except in elderly patients. 14% of the haemorrhages occurred in inpatients already in hospital for some other reason. In 27% of cases (37% female, 19% male) patients were aged over 80. Overall mortality was 14% (11% in emergency admissions and 33% in haemorrhage in inpatients). In the emergency admissions, 65% of deaths in those aged under 80 were associated with malignancy or organ failure at presentation. Mortality for patients under 60 in the absence of malignancy or organ failure at presentation was 0.8%. The incidence of acute upper gastrointestinal haemorrhage is twice that previously reported in England and similar to that reported in Scotland. The incidence increases appreciably with age. Although the proportion of elderly patients continues to rise and mortality increases steeply with age, age standardised mortality is lower than in earlier studies. Deaths occurred almost exclusively in very old patients or those with severe comorbidity.
Article
Full-text available
After endoscopic treatment of bleeding peptic ulcers, bleeding recurs in 15 to 20 percent of patients. We assessed whether the use of a high dose of a proton-pump inhibitor would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels were treated with an epinephrine injection followed by thermocoagulation. After hemostasis had been achieved, they were randomly assigned in a double-blind fashion to receive omeprazole (given as a bolus intravenous injection of 80 mg followed by an infusion of 8 mg per hour for 72 hours) or placebo. After the infusion, all patients were given 20 mg of omeprazole orally per day for eight weeks. The primary end point was recurrent bleeding within 30 days after endoscopy. We enrolled 240 patients, 120 in each group. Bleeding recurred within 30 days in 8 patients (6.7 percent) in the omeprazole group, as compared with 27 (22.5 percent) in the placebo group (hazard ratio, 3.9; 95 percent confidence interval, 1.7 to 9.0). Most episodes of recurrent bleeding occurred during the first three days, which made up the infusion period (5 in the omeprazole group and 24 in the placebo group, P<0.001). Three patients in the omeprazole group and nine in the placebo group underwent surgery (P=0.14). Five patients (4.2 percent) in the omeprazole group and 12 (10 percent) in the placebo group died within 30 days after endoscopy (P=0.13). After endoscopic treatment of bleeding peptic ulcers, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding.
Article
Full-text available
Aim: Recurrent bleeding after initial haemostasis is an important factor that directly relates to the outcome in the management of peptic ulcer bleeding. Conflicting reports have been published concerning the effectiveness of scheduled second therapeutic endoscopy on ulcer rebleeding. We investigate the use of scheduled second endoscopy with appropriate therapy on peptic ulcer rebleeding. From August 1999 to January 2001, we prospectively randomised patients who had endoscopically confirmed bleeding peptic ulcer with stigmata of acute bleeding, visible vessel, or adherent clot into two groups. Endoscopic therapy was standardised to initial epinephrine injection and subsequent heater probe application. The study group (n = 100) received scheduled second endoscopy 16-24 hours after initial haemostasis, and further therapy was applied if endoscopic stigmata persisted, as above. The control group (n = 94) were observed closely. Those patients that developed rebleeding in either group underwent operation if further endoscopic therapy failed. Outcome measures included ulcer rebleeding, transfusion, duration of stay, and mortality. After initial endoscopic haemostasis, 194 eligible patients were randomised into two groups. Thirteen patients in the control group developed recurrent bleeding within 30 days while five patients in the study group sustained recurrent bleeding (p = 0.0314) (relative risks 0.33, 95% confidence interval 0.1-0.96). The number of patients that required surgery for recurrent bleeding was six in the control group and one in the study group (p = 0.05). There was no difference in duration of hospital stay, transfusion, or mortality between the two groups. A scheduled repeat endoscopy with appropriate therapy 16-24 hours after initial endoscopic haemostasis reduces the number of cases of recurrent bleeding.
Article
Background & Aims: NSAIDs and Helicobacter pylori are risk factors for the development of peptic ulcers. A prospective study was conducted to determine prevalence of NSAID use, H pylori infection, and outcome of peptic ulcer bleeding. Methods: In 2000, data of all 361 patients presenting with peptic ulcer bleeding were prospectively collected in a defined geographical area, including 14 hospitals, and serving a catch area of 1.68 million persons. Follow-up data after a mean of 31 months were obtained from 211 patients. Results: The overall incidence was 21.5 cases per 100,000 persons. Mean age of the group was 70.9 years, 55% were male, and 41% had severe or life-threatening comorbidity. NSAIDs were used by 52%, and in only 17% concomitant acid suppressive therapy was given. H pylori infection was tested in 64%. Of the patients tested for H pylori, 43% were positive. Twenty-three percent were H pylori negative and not using NSAIDs. Rebleeding during initial admission occurred in 19%. Mortality during initial admission was 14%. During follow-up mortality was high, 29%. Conclusions: Half of all ulcer bleeding was associated with NSAID use. Only a minority of NSAID users used concomitant acid suppressive therapy. H pylori is not assessed systematically in all patients with ulcer bleeding. Almost a quarter of the ulcers were associated with neither H pylori infection nor NSAID use. Mortality, both during hospitalization and follow-up, was substantial.
Article
The late outcome of patients who present with major peptic ulcer haemorrhage is unclear. An examination was made of the hypothesis that prognosis may be poor because many such patients have severe co-morbid diseases. Some 121 patients treated endoscopically for severe peptic ulcer haemorrhage were followed for a median of 36 (range 30-76) months and outcome was compared with that of age- and sex-matched controls. Thirty patients (25 per cent) died during the follow-up period and Kaplan-Meier plots showed reduced survival in patients with ulcers (P < 0.01). Death was restricted largely to patients who had co-morbid diseases. Eight of the remaining 91 patients had further peptic ulcer bleeding; two of these were taking maintenance acid-reducing therapy and only one had significant dyspepsia before rebleeding. Eighty-three per cent of surviving patients had little or no dyspepsia. The late prognosis of patients who present with major ulcer haemorrhage is poor, but most deaths are a consequence of co-morbid disease and not recurrent ulcer bleeding. Most patients have little dyspepsia and those who rebleed are largely free from dyspepsia.
Article
Determine the relation of race and gender to outcome from bleeding peptic ulcer. Retrospective cohort study. All acute care hospitals in the United States. A 100% sample of hospitalized Medicare beneficiaries older than 64 years (n = 82,868) with a primary discharge diagnosis of peptic ulcer with hemorrhage. Surgical treatment was performed in 6.9% of patients, 30-day mortality was 8.5%, and average length of stay was 9.4 days. Surgery was somewhat more common in men than women (7.3% vs 6.5%, p < .001), and in whites than African Americans (6.9% vs 6.3%, p < .001), but neither race nor gender was associated with surgery in multivariable analysis adjusting for potentially confounding factors. Mortality rates were similar in African Americans and whites (8.5%), and somewhat higher in men than women (10.7% vs 9.3%, p < .001). In multivariable analysis, there was no difference in mortality across gender and racial groups. Although unadjusted and adjusted lengths of stay were longer for African Americans and shorter for men, the differences were modest (i.e., 16% increase and 6% decrease in multivariable analysis, respectively, p < .0001). In this national sample, there is no significant gender or racial difference in therapy and outcome for patients with hemorrhagic peptic ulcer. The findings raise the possibility that studies that have shown race and gender differences in management of coronary artery disease and cancer may not be generalizable to other common diagnoses.
Article
Mortality after peptic ulcer bleeding (PUB) is high in elderly patients despite therapeutic advances. Little is known about what actually determines rebleeding and mortality. The objective of this study was to investigate which factors may have an independent influence upon rebleeding and mortality in patients with PUB. Prospective cohort study. Patients, above 60 years of age, hospitalized due to an endoscopically verified acute PUB were included in the study (n = 508). The occurrence of rebleeding within 3 days and mortality within 30 days was registered for all patients. A predefined set of variables with a potential to influence rebleeding and mortality was analysed in a multiple logistic regression model. Odds ratios (with confidence intervals) for all predefined variables with respect to influence upon rebleeding and mortality, respectively. The risk of rebleeding was significantly increased with greater age and if the patient was suffering from shock, while omeprazole infusion, acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drug (NSAID) intake before admission and gastric ulcer localization were associated with a lower risk. Mortality was significantly increased with greater age, heart disease and blood pressure < 100 mmHg at admission. Previous ulcer history and the presence of a Forrest class IIa ulcer significantly reduced this risk. Elderly patients in shock admitted due to their first peptic ulcer bleeding run the greatest risk of an unfavourable outcome.
Article
Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause peptic ulcer disease and upper GI bleeding. Acid suppression medications effectively treat NSAID-induced ulcers. However, it is unknown what effect the availability of proton pump inhibitors and over-the-counter preparations of NSAIDs and histamine type 2 receptor antagonists have had on population rates of hospitalization and mortality from GI toxicity. This study examines trends in hospitalization and mortality rates from GI toxicity during the 1990s. We performed an analysis of secular trends of hospitalization and mortality rates from peptic ulcer disease, upper GI bleeding, and any GI bleeding using data from the National Hospital Discharge Survey, comparing them with sales of NSAIDs, aspirin, and acid suppression medications from 1992 to 1999. From 1992 to 1999, annual rates of hospitalization and mortality per 100,000 population for peptic ulcer disease declined from 205 to 165 and 7.7 to 6.0, respectively; calendar year was negatively correlated with both peptic ulcer disease hospitalization rates (p = -0.88, p = 0.007) and mortality rates (p = -0.71, p = 0.058). In contrast, these correlations did not reach statistical significance for upper or any GI bleeding (p > 0.1 for all comparisons). Sales of acid suppression medications were negatively correlated with peptic ulcer disease hospitalization rates (p = -0.76, p = 0.037) and mortality rates (p = -0.83, p = 0.015). Sales of NSAIDs were not positively correlated with hospitalization or mortality rates from peptic ulcer disease or GI bleeding (p > 0.2 for all comparisons). Despite changing patterns of use of NSAIDs and acid suppression medications during the 1990s, mortality rates from GI bleeding and peptic ulcer disease have been relatively stable, with an apparent decline in hospitalization rates and mortality from peptic ulcer disease. Changing rates of peptic ulcer disease morbidity and mortality were temporally related to increasing sales of antiulcerants but not to change in sales of NSAIDs.
Article
Two recent randomized, controlled trials have demonstrated efficacy for combination endoscopic therapy in the management of bleeding peptic ulcer with adherent clot. The aim of this study was to determine the effectiveness of this technique in a clinical practice setting. Medical records of consecutive patients, seen from January 1992 through December 1999, with severe ulcer hemorrhage and non-bleeding adherent clots resistant to target irrigation were reviewed. The decision for combination endoscopic therapy (epinephrine injection, removal of adherent clot, treatment of underlying stigmata) or medical therapy was left to the discretion of the endoscopist. Of 244 patients with adherent clots, 138 (56.6%) had endoscopic therapy and 106 (43.4%) were managed with medical therapy alone. The baseline characteristics of the two groups were similar, except for older age in the endoscopic therapy group. Recurrence of bleeding within 7 days of endoscopy was significantly less frequent in the endoscopic therapy group than the medical therapy group (respectively, 8.7% vs. 27.4%; adjusted odds ratio 0.07 95% CI [0.02, 0.22], p<0.001). Median hospital stay (6.0 vs. 8.0 days; p<0.001), median number of red blood cell transfusions after endoscopy (2.0 vs. 3.0 units; p=0.01), the need for repeat endoscopy (9.4% vs. 26.4%; p<0.001), and recurrent bleeding within 30 days (10.1% vs. 28.3%; p<0.001) were significantly lower in the endoscopic therapy group. In addition, the need for ulcer surgery (5.8% vs. 9.4%; p=0.28) and 30-day mortality (3.6% vs. 7.5%; p=0.18) were lower in the endoscopic therapy group, although these differences were not statistically significant. Endoscopic complications were uncommon (1.4% vs. 0.9%; p=1.00). Combination endoscopic treatment of ulcers with an adherent clot was associated with a significant reduction in recurrent ulcer hemorrhage compared with medical therapy alone. These findings confirm that the efficacy of combination endoscopic therapy demonstrated in carefully designed, randomized, controlled clinical trials can be reproduced when this technique is applied in a clinical practice setting. However, combination therapy did not significantly reduce the need for ulcer surgery or 30-day mortality.
Article
Despite the introduction of effective medical treatment of peptic ulcer disease, bleeding is still a frequent complication. The aim of this study was to investigate whether the incidence and the risk profile of peptic ulcer haemorrhage have changed within a 10-year period. In a prospective epidemiological and observational study the incidence and risk profile of peptic ulcer haemorrhage in Düsseldorf, Germany were compared between two time periods (period A: 1.3.89-28.2.90 and period B: 1.4.99-31.3.2000), involving nine hospitals with both surgical and medical departments. Patients with proven peptic ulcer haemorrhage at endoscopy or operation were included in the study; those with bleeding under defined severe stress conditions were excluded. No differences in bleeding ulcer incidence were observed between periods A and B (51.4 per 100,000 person-years versus 48.7), or for duodenal ulcer (24.9 versus 25.7) or for gastric ulcer bleeding (26.5 versus 23.0). A marked increase in incidence rates was observed with increasing age. In period B, patients with bleeding ulcers were older (56% versus 41% 70 years or older), were usually taking non-steroidal anti-inflammatory drugs (NSAIDs) (45% versus 27%) and were less likely to have a history of ulcer (25% versus 59%) compared with patients in period A. The persisting high incidence of peptic ulcer disease is a superimposing of two trends: a higher incidence in the growing population of elderly patient with a higher intake of NSAIDs and a lower incidence among younger patients due to a decrease in incidence and improved medical treatment.