Ulcer Bleeding

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copy 2012 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY

ACG PRACTICE GUIDELINES

Ulcers are the most common cause o hospitalization or upper

gastrointestinal bleeding (UGIB) and the vast majority o clini-

cal trials o therapy or nonvariceal UGIB ocus on ulcer diseaseTis guideline provides recommendations or the management

o patients with overt UGIB due to gastric or duodenal ulcers

ldquoOvertrdquo indicates that patients present with symptoms o he-

matemesis melena andor hematochezia We 1047297rst discuss the

initial management o UGIB in patients without known portal

hypertension including initial assessment and risk strati1047297cation

pre-endoscopic use o medications and gastric lavage and tim-

ing o endoscopy We then ocus on the endoscopic and medical

management o ulcer disease including endoscopic 1047297ndings and

their prognostic implications endoscopic hemostatic therapy

post-endoscopic medical therapy and disposition and preven-

tion o recurrent ulcer bleeding

Each section o the document presents the key recommenda-tions related to the section topic ollowed by a summary o the

supporting evidence A summary o recommendations is provided

in Table 1

A search o MEDLINE via the OVID interace using the

MeSH term ldquogastrointestinal hemorrhagerdquo limited to ldquoall clinical

trialsrdquo and ldquometa-analysisrdquo or years 1966ndash2010 without lan-

guage restriction as well as review o clinical trials and reviews

known to the authors were perormed or preparation o thisdocument Te GRADE system was used to grade the strength

o recommendations and the quality o evidence (1) Te quality

o evidence which in1047298uences the strength o recommendation

ranges rom ldquohighrdquo (urther research is very unlikely to change

our con1047297dence in the estimate o effect) to ldquomoderaterdquo (urther

research is likely to have an important impact on our con1047297dence

in the estimate o effect and may change the estimate) to ldquolowrdquo

(urther research is very likely to have an important impact on

our con1047297dence in the estimate o effect and is likely to change the

estimate) and ldquo very lowrdquo (any estimate o effect is very uncer-

tain) Te strength o a recommendation is graded as strong

when the desirable effects o an intervention clearly outweigh

the undesirable effects and is graded as conditional when uncer-tainty exists about the trade-offs (1) In addition to quality o

evidence and balance between desirable and undesirable effects

other actors affecting the strength o recommendation include

variability in values and preerences o patients and whether an

intervention represents a wise use o resources (1)

Management of Patients With Ulcer Bleeding

Loren Laine MD1 2 and Dennis M Jensen MD3ndash5

This guideline presents recommendations for the step-wise management of patients with overt upper gastrointestinal

bleeding Hemodynamic status is first assessed and resuscitation initiated as needed Patients are risk-stratified

based on features such as hemodynamic status comorbidities age and laboratory tests Pre-endoscopic

erythromycin is considered to increase diagnostic yield at first endoscopy Pre-endoscopic proton pump inhibitor

(PPI) may be considered to decrease the need for endoscopic therapy but does not improve clinical outcomes Upper

endoscopy is generally performed within 24 h The endoscopic features of ulcers direct further management Patients

with active bleeding or non-bleeding visible vessels receive endoscopic therapy (eg bipolar electrocoagulation

heater probe sclerosant clips) and those with an adherent clot may receive endoscopic therapy these patients then

receive intravenous PPI with a bolus followed by continuous infusion Patients with flat spots or clean-based ulcers

do not require endoscopic therapy or intensive PPI therapy Recurrent bleeding after endoscopic therapy is treated

with a second endoscopic treatment if bleeding persists or recurs treatment with surgery or interventional radiologyis undertaken Prevention of recurrent bleeding is based on the etiology of the bleeding ulcer H pylori is eradicated

and after cure is documented anti-ulcer therapy is generally not given Nonsteroidal anti-inflammatory drugs (NSAIDs)

are stopped if they must be resumed low-dose COX-2-selective NSAID plus PPI is used Patients with established

cardiovascular disease who require aspirin should start PPI and generally re-institute aspirin soon after bleeding

ceases (within 7 days and ideally 1ndash3 days) Patients with idiopathic ulcers receive long-term anti-ulcer therapy

Am J Gastroenterol 2012 107345ndash360 doi101038ajg2011480 published online 7 February 2012

1 Section of Digestive Diseases Yale University School of Medicine New Haven Connecticut USA 2 VA Connecticut Healthcare System New Haven

Connecticut USA 3 David Geffen School of Medicine University of California Los Angeles Los Angeles California USA 4 CURE Digestive Diseases

Research Center Los Angeles California USA 5 VA Greater Los Angeles Healthcare System Los Angeles California USA Correspondence Loren Laine

MD Section of Digestive Diseases Yale University School of Medicine 333 Cedar Street 1080 LMP New Haven Connecticut 06520-8019 USA

E-mail lorenlaineyaleeduReceived 31 July 2011 accepted 21 December 2011

CME



The American Journal of GASTROENTEROLOGY VOLUME 107 | MARCH 2012 wwwamjgastrocom

46 Laine and Jensen

Table 1 Summary and strength of recommendations

Initial assessment and risk stratification

1 Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun as needed (Strong recommendation)

2 Blood transfusions should target hemoglobin ge 7 g dl with higher hemoglobins targeted in patients with clinical evidence of intravascular volume depletion

or comorbidities such as coronary artery disease (Conditional recommendation)

3 Risk assessment should be performed to stratify patients into higher and lower risk categories and may assist in initial decisions such as timing of

endoscopy time of discharge and level of care (Conditional recommendation)

4 Discharge from the emergency department without inpatient endoscopy may be considered in patients with urea nitrogen lt 182 mg dl hemoglobin

ge 130 g dl for men (120 g dl for women) systolic blood pressure ge 110 mm Hg pulse lt 100 beats min and absence of melena syncope cardiac failure

and liver disease as they have lt 1 chance of requiring intervention (Conditional recommendation)

Pre-endoscopic medical therapy

5 Intravenous infusion of erythromycin (250 mg ~30 min before endoscopy) should be considered to improve diagnostic yield and decrease the need for

repeat endoscopy However erythromycin has not consistently been shown to improve clinical outcomes (Conditional recommendation)

6 Pre-endoscopic intravenous PPI (eg 80 mg bolus followed by 8 mg h infusion) may be considered to decrease the proportion of patients who have

higher risk stigmata of hemorrhage at endoscopy and who receive endoscopic therapy However PPIs do not improve clinical outcomes such as further

bleeding surgery or death (Conditional recommendation)

7 If endoscopy will be delayed or cannot be performed intravenous PPI is recommended to reduce further bleeding (Conditional recommendation)

Gastric lavage

8 Nasogastric or orogastric lavage is not required in patients with UGIB for diagnosis prognosis visualization or therapeutic effect (Conditional recommendation)

Timing of endoscopy

9 Patients with UGIB should generally undergo endoscopy within 24 h of admission following resuscitative efforts to optimize hemodynamic parameters and

other medical problems (Conditional recommendation)

10 In patients who are hemodynamically stable and without serious comorbidities endoscopy should be performed as soon as possible in a non-emergent

setting to identify the substantial proportion of patients with low-risk endoscopic findings who can be safely discharged (Conditional recommendation)

11 In patients with higher risk clinical features (eg tachycardia hypotension bloody emesis or nasogastric aspirate in hospital) endoscopy within 12 h may

be considered to potentially improve clinical outcomes (Conditional recommendation)

Endoscopic diagnosis

12 Stigmata of recent hemorrhage should be recorded as they predict risk of further bleeding and guide management decisions The stigmata in descending

risk of further bleeding are active spurting non-bleeding visible vessel active oozing adherent clot flat pigmented spot and clean base (Strong recommendation)

Endoscopic therapy

13 Endoscopic therapy should be provided to patients with active spurting or oozing bleeding or a non-bleeding visible vessel (Strong recommendation)

14 Endoscopic therapy may be considered for patients with an adherent clot resistant to vigorous irrigation Benefit may be greater in patients with clinical fea-

tures potentially associated with a higher risk of rebleeding (eg older age concurrent illness inpatient at time bleeding began) (Conditional recommendation)

15 Endoscopic therapy should not be provided to patients who have an ulcer with a clean base or a flat pigmented spot (Strong recommendation)

16 Epinephrine therapy should not be used alone If used it should be combined with a second modality (Strong recommendation)

17 Thermal therapy with bipolar electrocoagulation or heater probe and injection of sclerosant (eg absolute alcohol) are recommended because they

reduce further bleeding need for surgery and mortality (Strong recommendation)

18 Clips are recommended because they appear to decrease further bleeding and need for surgery However comparisons of clips vs other therapies yield

variable results and currently used clips have not been well studied (Conditional recommendation)

19 For the subset of patients with actively bleeding ulcers thermal therapy or epinephrine plus a second modality may be preferred over clips or sclerosant

alone to achieve initial hemostasis (Conditional recommendation)

Medical therapy after endoscopy

20 After successful endoscopic hemostasis intravenous PPI therapy with 80 mg bolus followed by 8 mgh continuous infusion for 72 h should be given to

patients who have an ulcer with active bleeding a non-bleeding visible vessel or an adherent clot (Strong recommendation)

21 Patients with ulcers that have flat pigmented spots or clean bases can receive standard PPI therapy (eg oral PPI once daily) (Strong recommendation)

Repeat endoscopy

22 Routine second-look endoscopy in which repeat endoscopy is performed 24 h after initial endoscopic hemostatic therapy is not recommended

(Conditional recommendation)

23 Repeat endoscopy should be performed in patients with clinical evidence of recurrent bleeding and hemostatic therapy should be applied in those with

higher risk stigmata of hemorrhage (Strong recommendation)

24 If further bleeding occurs after a second endoscopic therapeutic session surgery or interventional radiology with transcathether arterial embolization is

generally employed (Conditional recommendation)




3Management of Patients With Ulcer Bleeding

in whom the hemoglobin is ldquoarti1047297ciallyrdquo elevated beore repletion

with intravascular 1047298uid Intubation may be considered to protect

the airway and prevent aspiration in patients with severe ongoing

hematemesis andor altered mental status it may also be neces-

sary in some patients (eg those with comorbidities) to saely and

effectively provide sedation or endoscopy

Risk assessment o patients is clinically useul to determine which

patients are at higher risk o urther bleeding or death and may inorm

management decisions such as timing o endoscopy time o discharge

and level o care (eg ward vs step-down vs intensive care)

Instruments used to assess risk include the pre-endo-

scopic Rockall score (7) and the Blatchord score (8) Te pre-endoscopic Rockall score (range 0ndash7) uses only clinical data avail-

able immediately at presentation which are related to the sever-

ity o the bleeding episode (systolic blood pressure and pulse)

and to the patient (age and comorbidities) It has been shown

to predict the risk o urther bleeding and death in a population

o patients hospitalized with UGIB (7) Te Blatchord score

(range 0ndash23) uses clinical data (systolic blood pressure pulse

melena syncope hepatic disease and heart ailure) and labora-

tory data (hemoglobin and blood urea nitrogen) available early

afer admission It has been shown to predict the risk o inter-

vention (transusion and endoscopic or surgical therapy) and death

in a population o patients presenting to hospital with UGIB (8)

In general risk assessment with scoring systems such as Blatch-ord or Rockall is not able to unequivocally identiy individual

patients who will require intervention with one exception Patients

with a Blatchord score o 0 (urea nitrogen lt 182 mgdl hemo-

globin ge 130 gdl or men (120 gdl or women) systolic blood

pressure ge 110 mm Hg pulse lt 100 beatsmin absence o melena

syncope cardiac ailure and liver disease) which may occur in up

to ~5ndash20 o those presenting with UGIB have lt 1 chance o

requiring intervention (8ndash11)

In a prospective series Stanley et al (9) did not admit

patients presenting to emergency departments with UGIB who

had Blatchord scores o 0 unless necessary or other reasons O

INITIAL ASSESSMENT AND RISK STRATIFICATION

Recommendations

1 Hemodynamic status should be assessed immediately upon pre-

sentation and resuscitative measures begun as needed (Strong recom-

mendation low-quality evidence)

2 Blood transusions should target hemoglobin ge 7 g dl with higher

hemoglobins targeted in patients with clinical evidence o intravascu-

lar volume depletion or comorbidities such as coronary artery disease

(Conditional recommendation low-to-moderate-quality evidence)

3 Risk assessment should be perormed to stratiy patients into

higher and lower risk categories and may assist in initial decisions

such as timing o endoscopy time o discharge and level o care(Conditional recommendation low-quality evidence)

4 Discharge rom the emergency department without inpatient

endoscopy may be considered in patients with urea nitrogen lt 182

mg dl hemoglobinge 130 g dl or men (120 g dl or women) systolic

blood pressure ge 110 mm Hg pulse lt 100 beats min and absence

o melena syncope cardiac ailure and liver disease as they

have lt 1 chance o requiring intervention (Conditional recom-


Summary of evidence Based on other models o hemorrhage (2)

the 1047297rst step in management o patients presenting with overt

upper gastrointestinal bleeding (UGIB) is assessment o hemody-

namic status and initiation o resuscitative measures as needed Inaddition to intravenous 1047298uids transusion o red blood cells may be

required Randomized trials in euvolemic patients without current

bleeding (3) and in cirrhotics with UGIB (4) indicate that transu-

sions should be given to maintain hemoglobin ge 7 gdl A restric-

tive transusion policy is also supported by an older randomized

trial o 50 patients without known varices in which patients trans-

used ge 2 units within 24 h o admission had signi1047297cantly more

rebleeding than those not transused unless Hgb was lt 8 gdl (5)

Higher hemoglobin levels may need to be targeted in patients with

other illnesses (eg coronary artery disease) (6) and in those with

intravascular volume depletion (ie hypotension and tachycardia)

Table 1 Continued

Hospitalization

25 Patients with high-risk stigmata (active bleeding visible vessels clots) should generally be hospitalized for 3 days assuming no rebleeding and no other

reason for hospitalization They may be fed clear liquids soon after endoscopy (Conditional recommendation)

26 Patients with clean-based ulcers may receive a regular diet and be discharged after endoscopy assuming they are hemodynamically stable their hemo-

globin is stable they have no other medical problems and they have a residence where they can be observed by a responsible adult (Strong recommendation)

Long-term prevention of recurrent bleeding ulcers

27 Patients with H pylori -associated bleeding ulcers should receive H pylori therapy After documentation of eradication maintenance antisecretory

therapy is not needed unless the patient also requires NSAIDs or antithrombotics (Strong recommendation)

28 In patients with NSAID-associated bleeding ulcers the need for NSAIDs should be carefully assessed and NSAIDs should not be resumed if possible In

patients who must resume NSAIDs a COX-2 selective NSAID at the lowest effective dose plus daily PPI is recommended (Strong recommendation)

29 In patients with low-dose aspirin-associated bleeding ulcers the need for aspirin should be assessed If given for secondary prevention (ie established

cardiovascular disease) then aspirin should be resumed as soon as possible after bleeding ceases in most patients ideally within 1ndash3 days and certainly

within 7 days Long-term daily PPI therapy should also be provided If given for primary prevention (ie no established cardiovascular disease) anti-platelet

therapy likely should not be resumed in most patients (Conditional recommendation)

30 In patients with idiopathic (non-H pylori non-NSAID) ulcers long-term antiulcer therapy (eg daily PPI) is recommended (Conditional recommendation)

PPI proton pump inhibitor NSAID non-steroidal anti-inflammatory drug UGIB upper gastrointestinal bleeding




48 Laine and Jensen

123 patients with scores o 0 84 were not admitted Among the

23 patients receiving outpatient endoscopy no ulcers varices

or malignancies were ound and no inter ventions were needed

Among the remainder none were readmitted with UGIB or died

during ge 6 months o ollow-up Tus discharge rom the emer-

gency department without inpatient endoscopy may be consid-

ered in very low-risk patients with Blatchord scores o 0

PRE-ENDOSCOPIC MEDICAL THERAPY

Prokinetic therapy

Recommendations

5 Intravenous inusion o erythromycin (250 mg ~30 min beore

endoscopy) should be considered to improve diagnostic yield and

decrease the need or repeat endoscopy However erythromycin has

not consistently been shown to improve clinical outcomes (Condi-

tional recommendation moderate-quality evidence)

Summary of evidence Prokinetic agents given beore endoscopy

have been proposed to improve visualization at endoscopy Treeully published randomized trials o erythromycin given intra-

venously beore endoscopy were identi1047297ed in a recent systematic re-

view (12) Inusions o erythromycin 250 mg or 3 mgkg were given

over 5 or 30 min and endoscopy was perormed 20ndash60 min afer the

inusion 1047297nished (13ndash15) All trials showed signi1047297cant improvement

in their primary end point related to visualization o mucosa

However a more clinically appropriate question is whether

use o erythromycin translates into more diagnoses made at

initial endoscopy or better clinical outcomes Meta-analysis o

these three trials ( 13ndash15) reveals a very modest but signi1047297cant

bene1047297t (relative risk (RR) = 113 102ndash126 number needed to

treat (NN) = 9) in diagnosis at 1047297rst endoscopy Erythromycindid not signi1047297cantly reduce clinical outcomes such as blood

transusions hospital stay or surgery but did decrease the pro-

portion o patients undergoing a second endoscopy (12) Only

two abstracts assessing metoclopramide were identi1047297ed in this

meta-analysis and no signi1047297cant bene1047297ts were ound in this

small sample (12)

Since this meta-analysis a study reporting on the non-rand-

omized cohort o patients with variceal bleeding rom within a ran-

domized trial ound better visualization and shorter hospital stay

with erythromycin but no signi1047297cant decreases in transusions or

repeat endoscopy (16) A randomized comparison o erythromy-

cin standard-bore nasogastric (NG) tube or erythromycin plus

NG tube in 253 patients with UGIB revealed no signi1047297cant di-erences in visualization diagnosis at 1047297rst endoscopy second-look

endoscopy urther bleeding or transusions (17)

Proton pump inhibitor therapy

Recommendations

6 Pre-endoscopic intravenous proton pump inhibitor (PPI) (eg 80 mg

bolus ollowed by 8 mg h inusion) may be considered to decrease the

proportion o patients who have higher risk stigmata o hemorrhage

at endoscopy and who receive endoscopic therapy However PPIs do

not improve clinical outcomes such as urther bleeding surgery or

death (Conditional recommendation high-quality evidence)

7 I endoscopy will be delayed or cannot be perormed intravenous

PPI is recommended to reduce urther bleeding (Conditional recom-

mendation moderate-quality evidence)

Summary of evidence A Cochrane meta-analysis o six rand-

omized trials (N = 2223) o pre-endoscopic PPI therapy ound no

signi1047297cant differences between PPI and control in mortality (61

vs 55 odds ratio (OR) = 112 072ndash173) rebleeding (139 vs

166 OR = 081 061ndash109) or surgery (99 vs 102 OR = 096

068ndash135) (18) PPI therapy signi1047297cantly reduced the proportion

o participants with higher risk stigmata o hemorrhage (active

bleeding non-bleeding visible vessel and adherent clot) at index

endoscopy (372 vs 465 OR = 067 054ndash084) and undergoing

endoscopic therapy at index endoscopy (86 vs 117 OR = 068

050ndash093) Similar results were seen in the highest quality study

which also was the only study employing high-dose bolus and

continuous inusion intravenous PPI (19) Endoscopic therapy

was perormed in 191 vs 284 (P = 0007) and among those

with ulcers active bleeding was signi1047297cantly less common (64 vs 147 P = 001) and clean-based ulcers more common (642

vs 474 P = 0001) with PPI therapy PPI therapy should be

discontinued afer endoscopy unless the patient has a source or

which PPIs may be bene1047297cial (eg ulcers and erosions)

A Cochrane meta-analysis o randomized trials o patients with

UGIB who did not consistently receive endoscopic hemostatic

therapy reported that PPI therapy was associated with reduced

rebleeding (OR = 038 018ndash081 (with signi1047297cant heterogeneity)

NN = 10) and surgery (OR = 062 044ndash088 NN = 17) but not

mortality (20) Tis suggests that i endoscopy will be delayed or

cannot be perormed PPI therapy may improve clinical outcomes

Gastric lavage

Recommendations

8 NG or orogastric lavage is not required in patients with UGIB

or diagnosis prognosis visualization or therapeutic effect (Condi-

tional recommendation low-quality evidence)

Summary of evidence A variety o reasons have been advanced to

perorm NG lavage in patients with gastrointestinal (GI) bleeding

to determine i the source o bleeding is in the upper GI tract to

provide prognostic inormation to clear blood and clots and

allow better visualization at endoscopy and to treat UGIB

Documentation of a UGI source NG aspirates with blood or co-ee-ground material clearly document UGIB and a bloody NG

aspirate increases the likelihood o 1047297nding active bleeding or a

non-bleeding visible vessel as compared with coffee-grounds or

a clear NG aspirate (2122) However a clear or bile-stained NG

aspirate may be seen in up to 18 o patients with an upper GI

source (22ndash27) For example in a Canadian UGIB registry 13

o patients with UGIB had a clear or bile-stained aspirate 15

o patients with a clearbile-stained aspirate had active bleeding

or non-bleeding visible vessel compared with 23 with coffee-

grounds and 45 with bloody aspirates (22) In a prospective

study o patients presenting with hematochezia plus hypotension





10 In patients who are hemodynamically stable and without

serious comorbidities endoscopy should be perormed as soon as

possible in a non-emergent setting to identiy the substantial pro-

portion o patients with low-risk endoscopic 1047297ndings who can

be saely discharged (Conditional recommendation moderate-

quality evidence)

11 In patients with higher risk clinical eatures (eg tachycardia

hypotension bloody emesis or NG aspirate in hospital) endoscopy

within 12 h may be considered to potentially improve clinical

outcomes (Conditional recommendation low-quality evidence)

Summary of evidence Early endoscopy has been variably de1047297ned

as endoscopy perormed within 2ndash24 h o presentation A variety

o observational studies and a ew randomized trials have assessed

this issue but marked variations in study design de1047297nitions end

points and methodologic rigor make synthesis o the results di-

1047297cult wo systematic reviews summarize these studies (3334)

Studies o early endoscopy consistently show that patients

undergoing endoscopy within 8 h o presentation have more high-risk stigmata (active bleeding visible vessels or adherent clots)

than those with later endoscopies (34) thereby increasing the

proportion who requires endoscopic therapy However obser-

vational studies do not document a bene1047297t in clinical outcomes

o endoscopy perormed within 2ndash12 h o presentation (3334)

Observational studies do suggest a bene1047297t o endoscopy within

24 h afer admission in terms o decreased length o stay (3536)

and surgical intervention (35) Tus endoscopy within 24 h

appears appropriate in a population hospitalized with UGIB

However risk strati1047297cation also may have a role in considerations

regarding timing o endoscopy

Low-risk patients Lee et al (37) perormed a randomized trial

comparing endoscopy within 2 h vs endoscopy within 48 h in

110 patients who were hemodynamically stable had no serious

comorbidity and had no reason to suspect variceal bleeding No

signi1047297cant improvements in end points such as bleeding surgery

or mortality were identi1047297ed However the length o hospital stay

post-discharge unplanned physician visits and costs were signi1047297-

cantly decreased in the early endoscopy group Forty-six percent

o patients in the early endoscopy group could be discharged

home immediately and had no rebleeding or repeat endoscopy

during the next month

In a second randomized trial comparing early endoscopy within

6 h vs within 48 h in 93 patients with hemodynamic stabilizationand absence o severe comorbidity no signi1047297cant bene1047297ts were

seen in clinical end points or in resource utilization (38) Although

discharge without hospitalization was recommended in the 40

o early endoscopy patients who met criteria or early discharge

this advice was ollowed in only 9 suggesting that the 1047297nancial

bene1047297t o early endoscopy can only be realized i physicians use the

results o endoscopy in making management decisions

Tus both studies suggest that early endoscopy in patients who

are hemodynamically stable and have no serious comorbidities

can potentially result in lower costs by allowing early discharge in

up to ~40ndash45 o patients supporting perormance o endoscopy

tachycardia dropping hemoglobin or transusion and a negative

NG aspirate 15 had an upper GI source (27) Although some

suggest that a non-bloody bile-stained aspirate indicates duodenal

contents were sampled and rules out a UGI source physicians are

incorrect about 50 o the time when they report bile in the aspi-

rate (25) In addition testing NG aspirates or occult blood is not

documented to be useul

Prognostic value Intuitively a persistently bloody NG aspirate

would seem likely to indicate a more severe UGIB episode An

NG aspirate with red blood is reported to be associated with more

severe bleeding (proportion requiring gt 5 units o blood and sur-

gery) (2122) and increases the chance o identiying high-risk stig-

mata at the time o endoscopy (2122) However whether a bloody

aspirate provides better prognostic inormation than other readily

available data such as blood pressure and pulse is not known In a

prospective trial in 325 patients the proportion with ldquoshockrdquo (systo-

lic blood pressure lt 100 mm Hg and pulse gt 100 beatsminute) cor-

related with the NG aspirate 1047297nding 11 with a clear aspirate 36with coffee-grounds and 60 with bloody aspirate (28)

Improvement of visualization Te standard small-bore NG tube

typically used or aspiration is not likely to effectively clear clots

rom the stomach A large-bore orogastric tube is more likely to

be successul in clearing the stomach with major UGIB A small

randomized comparison o a 40 French orogastric tube (with

sedation) vs no lavage in 38 patients showed a signi1047297cantly higher

proportion with excellent visualization in the undus (the primary

end point) and a trend in the antrum (P = 006) (29) Tere was

no signi1047297cant difference in the proportion with the bleeding

source de1047297ned (95 vs 83) Te use o a large-bore orogastrictube is diffi cult and uncomortable or patients and cannot be

recommended routinely

Endoscopic methods o aspiration designed to improve visu-

alization including use o a jumbo channel (6 mm) or an external

auxiliary device have been assessed in case series (3031) Further

study is needed to determine their potential role as compared with

prokinetic therapy and NG aspiration

Terapeutic effect Older textbooks reported that NG lavage

could stop bleeding in a majority o cases and recommended

use o iced saline However UGIB stops spontaneously in a

majority o patients without speci1047297c therapy and studies in dogs

with experimentally induced ulcers indicated that results withlavage are no better and may even be worse at temperatures o

0ndash4 degC (32)

ENDOSCOPY FOR DIAGNOSIS

Timing of endoscopy

Recommendations

9 Patients with UGIB should generally undergo endoscopy within

24 h o admission ollowing resuscitative efforts to optimize hemo-

dynamic parameters and other medical problems (Conditional

recommendation low-quality evidence)




50 Laine and Jensen

as soon as possible in patients with low-risk clinical eatures

However the lack o clinical bene1047297t argues against the need or

endoscopy in an emergent setting (eg ldquomiddle o the nightrdquo) or

low-risk patients Furthermore as mentioned earlier patients with

very low risk based on pre-endoscopic assessment (eg Blatchord

score o 0) may be considered or discharge rom the emergency

department without undergoing endoscopy (9)

High-risk patients In a randomized trial comparing endoscopy

within 12 h with endoscopy gt 12 h afer presentation without

exclusion o higher risk patients no signi1047297cant bene1047297t was iden-

ti1047297ed in bleeding surgery or mortality In subgroup analyses

patients who had a bloody NG aspirate pre-endoscopy (but not

those with clear or coffee-grounds aspirates) had signi1047297cantly

ewer units o blood transused and hospital days (28) As men-

tioned above a majority o these patients with a bloody aspirate

had systolic blood pressure lt 100 mm Hg and pulse gt 100 beats

minute A recent observational study also ound a signi1047297cantly

higher mortality in high-risk UGIB patients (Blatchord scorege 12) having endoscopy gt 13 h afer presentation (44) than in

those having earlier endoscopy (0 P lt 0001) (39) Multivariate

analysis ound that presentation-to-endoscopy time was the only

variable signi1047297cantly associated with mortality

Tus limited data rom subgroup analysis o a randomized trial

and an observational study raise the possibility that patients with

high-risk clinical eatures may have improved clinical outcomes i

endoscopy is perormed within 12 h o presentation

Risk of early endoscopy Te potential risk o endoscopy ofen

perormed during off hours in sick patients must be considered

A prospective non-randomized study indicated an increased risko oxygen desaturation in patients undergoing endoscopy within

2 h as compared with endoscopy at 2ndash24 h (40) Tis study high-

lights the act that early endoscopy has the potential to urther

increase complications i perormed too early beore appropriate

resuscitation and stabilization

Endoscopic diagnosis of ulcer and stigmata of recent hemorrhage

Recommendations

12 Stigmata o recent hemorrhage (SRH) should be recorded as they

predict risk o urther bleeding and guide management decisions Te

stigmata in descending risk o urther bleeding are active spurting

non-bleeding visible vessel active oozing adherent clot 1047298at pigmented

spot and clean base (Strong recommendation high-quality evidence)

Summary of evidence Te de1047297nition o an ulcer is a histological

one requiring extension into the submucosa or deeper In con-

trast erosions are breaks that remain con1047297ned to the mucosa Tis

is clinically relevant because serious bleeding does not occur rom

an erosion due to the absence o veins and arteries in the mucosa

Rather serious bleeding occurs when an ulcer erodes into vessels

in the submucosa or deeper Swain et al (41) assessed the histo-

logical characteristics o gastric ulcers with visible vessels in 27

patients who required surgery or urther bleeding and identi1047297ed

arteries in the ulcer base in 26 (96) o the 27 specimens

Although the de1047297nition o an ulcer relates to histological depth

in practice no objective measure o the depth o an ulcer is per-

ormed Currently the endoscopic diagnosis o an ulcer is based

on the interpretation o the endoscopist that unequivocal depth ispresent at endoscopic visualization

Ulcer surace area dimensions or diameter can be estimated with

the use o a device o known dimension such as an open biopsy

orceps Ulcers larger than 1ndash2 cm are associated with increased

rates o urther bleeding with conservative therapy and afer endo-

scopic therapy (42ndash44)

SRH are terms that describe the appearance o an ulcer base

at endoscopy in patients with ulcer bleeding SRH provide prog-

nostic inormation regarding the risk o rebleeding need or thera-

peutic intervention and death (4546) SRH are thereore used

to stratiy patients with ulcer bleeding and guide management

decisions including endoscopic and medical therapy admission vs discharge and level o care in hospital In the absence o clinical

evidence o bleeding however the presence o SRH does not

appear to be associated with a risk o subsequent bleeding (47)

Descriptive terms or SRH are generally used in North America

whereas the Forrest classi1047297cation is common in Europe and Asia

Te descriptive terms or SRH and corresponding Forrest classi1047297-

cations are shown in Table 2 with US prevalences Most patients

with ulcer bleeding have low risk characteristics o clean bases or

1047298at spots identi1047297ed at endoscopy (48) Active bleeding may be bro-

ken down into arterial spurting and oozing although most stud-

ies o prevalence have combined these categories A recent large

prospective trial ound that only 68 (17) o 397 patients enrolled

with actively bleeding ulcers had arterial spurting (49) Table 3 shows pooled rates o urther bleeding surgery and death without

endoscopic therapy strati1047297ed by SRH

Most studies and meta-analyses o ulcer hemorrhage outcomes

combine both spurting and oozing bleeding into an ldquoactive ulcer

bleedingrdquo category However results rom prospective trials suggest

they should be viewed separately because the risk o urther bleed-

ing with spurting probably is substantially higher than the risk with

oozing In non-randomized cohorts o patients receiving only con-

servative therapy (without endoscopic therapy) in two studies the

rate o urther bleeding requiring surgery was higher in those with

spurting than those with oozing (710 (70) vs 724 (29) and 58

Table 2 Classification and prevalences of stigmata of recent

hemorrhage in 2401 patients hospitalized with bleeding

ulcers at 72 US endoscopy centers (48)

Stigmata of

hemorrhage

Forrest

classification Prevalence

Active spurting bleeding IA 12 (spurting + oozing)

Active oozing bleeding IB

Non-bleeding visible

vessel

IIA 8

Adherent clot IIB 8

Flat pigmented spot IIC 16

Clean base III 55





14 Endoscopic therapy may be considered or patients with an adher-

ent clot resistant to vigorous irrigation Bene1047297t may be greater in

patients with clinical eatures potentially associated with a higher risk orebleeding (eg older age concurrent illness inpatient at time bleeding

began) (Conditional recommendation moderate-quality evidence)

15 Endoscopic therapy should not be provided to patients who have

an ulcer with a clean base or a 1047298at pigmented spot (Strong recom-

mendation high-quality evidence)

Summary of evidence Meta-analysis o trials o endoscopic ther-

apy vs no endoscopic therapy or patients with an actively bleed-

ing ulcer (spurting and oozing combined) shows a signi1047297cant

decrease in urther bleeding (RR = 029 020ndash043) with an NN

o only 2 (64) Te need or urgent intervention and surgery is

also signi1047297cantly decreased Meta-analysis o patients with a non-bleeding visible vessel in an ulcer reveals a signi1047297cant decrease in

urther bleeding (RR = 049 040ndash059 NN = 5) as well as urgent

intervention and surgery (64)

Although spurting and oozing bleeding are combined in most

randomized trials and meta-analyses as discussed above the rate

o urther bleeding appears to be substantially lower with oozing

Nevertheless the 39 pooled rate o rebleeding in patients who

were treated conservatively does support perorming endoscopic

therapy or oozing Better effi cacy may be expected afer endo-

scopic therapy in patients with oozing than in those with other

high-risk stigmata In a cohort o patients within the placebo arm

o a randomized trial o high-dose PPI vs placebo afer endoscopic

therapy the rates o urther bleeding at 72 h were lower with oozing(49) than with spurting (225) clots (177) or non-bleeding

visible vessels (113) (65)

Meta-analysis o randomized trials in patients with an adherent

clot does not show a signi1047297cant bene1047297t (RR = 031 006ndash177) (64)

However signi1047297cant heterogeneity is present among the studies

wo US trials reported signi1047297cant bene1047297t o endoscopic hemosta-

sis with pooled rebleeding rates or endoscopic vs medical therapy

o 3 vs 35 (6166) Te other studies rom Europe and Asia

showed no suggestion o any bene1047297t Te one study using therapy

matching current recommendations (vigorous irrigation bolus

and continuous inusion o PPI ollowing endoscopy) reported

(63) vs 735 (20)) (5051) In a study restricted to UGIB patients

requiring intensive care unit admission transusion-requiring

urther bleeding occurred in 2324 (88) with spurting and 328(11) o those with oozing (52) Data rom eight prospective trials

including UGIB patients with oozing treated conservatively with-

out endoscopic therapy reveal a pooled rate o urther bleeding o

39 (range 10ndash100) (505153ndash58) and urther bleeding requir-

ing emergency surgery in 26 (range 20ndash38) (50515556)

Marked differences can be seen across different reports in the rela-

tive proportions o SRH and may relate to several actors One poten-

tial explanation is the timing o the endoscopy as discussed above

with more high-risk SRH identi1047297ed with earlier endoscopy Another

potential explanation is inter-observer disagreement among endo-

scopists Considerable variability has been reported among endo-

scopists in classiying SRH rom photographs or video clips (5960)Improvements in agreement may be achieved with training (eg

instruction with review o photographs or videos atlases) (495961)

It is also possible that differing patient characteristics (eg severity

o comorbidities) may in1047298uence the prevalence o SRH

Another potential difference in reported proportions o SRH

may relate to variability in irrigation o clots Vigorous irrigation

with a water pump device will wash away overlying clot and reveal

underlying SRH in a substantial portion o patients Syringe irriga-

tion ollowed by only 10 s o water pump irrigation removed clots

in 33 o patients in one study (62) In another study water pump

irrigation or up to 5 min removed clots in 43 o patients reveal-

ing high-risk stigmata mandating endoscopic therapy in 30 and

low-risk stigmata in 13 no therapy was provided to the 57 withadherent clots and the rebleeding rate was only 8 (63) Tus vig-

orous irrigation o clots on an ulcer base is recommended to more

accurately determine underlying SRH and more accurately assess

the risk o rebleeding

ENDOSCOPIC THERAPY

Who should receive endoscopic therapy

Recommendations

13 Endoscopic therapy should be provided to patients with

active spurting or oozing bleeding or a non-bleeding visible vessel

(Strong recommendation high-quality evidence) (Figure 1 )

Active bleedingor non-bleedingvisible vessel

Endoscopic

therapy

IV PPIbolus + infusion

Adherent clot

May considerendoscopic

therapy


Flat spot orclean base

No endoscopic

therapy

Oral PPI

Figure 1 Recommended endoscopic and medical management based on

stigmata of hemorrhage in ulcer base IV intravenous PPI proton pump

inhibitor

Table 3 Stigmata of recent hemorrhage and average rates (with

ranges) of further bleeding surgery and mortality in prospective

trials without endoscopic therapy (45)

Stigmata

Further bleeding

(N =2994)

Surgery for

bleeding

(N =1499)

Mortality

(N =1387)

Active bleeding 55 (17ndash100) 35 (20ndash69) 11 (0ndash23)

Non-bleeding

visible vessel

43 (0ndash81) 34 (0ndash56) 11 (0ndash21)

Adherent clot 22 (14ndash36) 10 (5ndash12) 7 (0ndash10)

Flat pigmented

spot


Clean ulcer base 5 (0ndash10) 05 (0ndash3) 2 (0ndash3)




52 Laine and Jensen

no rebleeding in the 24 control patients with clots receiving only

medical therapy (67) Te reasons or the marked variation in

results are uncertain but potential explanations might include di-

erences in severity o comorbidities (US studies done primarily

in tertiary care centers) etiology o the ulcer disease (H pylori

ulcers may be more common outside the US) and response to

PPIs (greater in H pylori -positive patients and in Asia)

Patients with clean-based ulcers or 1047298at pigmented spots rarely

have serious recurrent bleeding (45) and thereore would not

derive signi1047297cant bene1047297t rom endoscopic therapy

What endoscopic therapies should be used

Recommendations

16 Epinephrine therapy should not be used alone I used it should

be combined with a second modality (Strong recommendation

high-quality evidence)

17 Termal therapy with bipolar electrocoagulation or heater probe

and injection o sclerosant (eg absolute alcohol) are recommended

because they decrease urther bleeding need or surgery and mor-tality (Strong recommendation high-quality evidence)

18 Clips are recommended because they appear to decrease urther

bleeding and need or surgery However comparisons o clips vs

other therapies yield variable results and currently used clips have not

been well studied (Conditional recommendation low-to-moderate

quality evidence)

19 For the subset o patients with actively bleeding ulcers thermal

therapy or epinephrine plus a second modality may be preerred over

clips or sclerosant alone to achieve initial hemostasis (Conditional

recommendation low-to-moderate-quality evidence)

Summary of evidence Te primary end point recommended intrials o UGIB is prevention o urther bleeding which includes

initial hemostasis in actively bleeding patients plus prevention o

rebleeding in those with initial hemostasis and in those without

active bleeding at presentation (68) Endoscopic therapies that

have shown effi cacy in randomized trials include thermal therapy

(eg bipolar electrocoagulation heater probe monopolar elec-

trocoagulation argon plasma coagulation and laser) injection

(epinephrine sclerosants (eg absolute ethanol polidocanol and

ethanolamine) thrombin or 1047297brin glue (thrombin plus 1047297brino-

gen)) and clips (64)

Randomized trials indicate epinephrine injection is effective

at achieving initial hemostasis in patients with active bleeding

with results not signi1047297cantly different rom other therapies (64)However epinephrine monotherapy is less effective than other

monotherapies in preventing urther bleeding (RR = 172 108ndash

278 NN = 9) and surgery based on meta-analysis o three trials

employing bipolar electrocoagulation clips or 1047297brin glue as com-

parators (64) Furthermore epinephrine plus a second modality

(eg bipolar electrocoagulation sclerosant and clip) is signi1047297cantly

more effective than epinephrine alone in reducing urther bleed-

ing (RR = 034 023ndash050 NN = 5) and surgery (64) However i

a second-look endoscopy is perormed and higher risk lesions are

retreated the bene1047297t o combined therapy vs epinephrine alone is

not seen (64)

Termal contact therapy with bipolar electrocoagulation or

heater probe is signi1047297cantly more effective than no endoscopic

therapy in achieving initial hemostasis (RR = 1170 515ndash2656)

reducing urther bleeding (RR = 044 036ndash054 NN = 4)

surgery and mortality (RR = 058 034ndash098 NN = 33) in a

meta-analysis o 15 randomized trials (64) No signi1047297cant di-

erences were seen in randomized trials comparing these two

thermal modalities Te term ldquomultipolar electrocoagulationrdquo

is used in some studies Te multipolar probe and other bipolar

probes all deliver bipolar electrocoagulation the difference in

terms relates only to the con1047297guration o the electrodes on the

probe tip Tus meta-analyses combine multipolar and bipolar

electrocoagulation trials

Results o two small studies suggested bene1047297t o epinephrine

plus bipolar electrocoagulation vs bipolar electrocoagulation

alone but results with thermal monotherapy were poorer in these

trials than most other studies (6970) A larger high-quality study

ound that injection o thrombin plus heater probe was not better

than heater probe alone (71) Tus although limited inormationsuggests that epinephrine ollowed by thermal contact therapy may

be more effi cacious than thermal therapy alone data are insuffi -

cient to recommend that thermal contact devices should not be

used alone as monotherapy

However there may be practical reasons to pre-inject epine-

phrine beore other therapies or speci1047297c SRH Anecdotally or

active bleeding injection o epinephrine may slow or stop bleed-

ing allowing improved visualization or application o subsequent

therapy In addition i clot removal is planned or adherent clots

resistant to irrigation pre-injection o epinephrine may reduce the

rate o severe bleeding induced by clot removal

Sclerosant injection also signi1047297cantly reduces urther bleeding(RR = 056 038ndash083 NN = 5) as well as surgery and mortality

as compared with no endoscopic therapy based on meta-analysis

o three randomized trials o absolute alcohol (64) Because the

volume o sclerosants must be limited due to concern or tissue

necrosis sclerosant therapy alone may not be optimal or actively

bleeding ulcers Among actively bleeding patients in a randomized

trial comparing absolute alcohol vs no therapy initial hemosta-

sis was achieved in only 46 with alcohol vs 8 in controls (64)

Epinephrine injection beore sclerosant therapy or actively bleed-

ing ulcers seems reasonable although this has not been compared

with sclerosant alone in randomized trials

rials comparing thermal therapy with sclerosant therapy show

no signi1047297cant difference in urther bleeding surgery or mortal-ity although thermal therapy showed signi1047297cantly ewer urgent

interventions (surgery repeat endoscopic therapy or interven-

tional radiology) and a trend to less urther bleeding (RR = 069

047ndash101) (64)

Clips have not been compared with no endoscopic therapy but

are more effective than injection o epinephrine or water in reduc-

ing urther bleeding and surgery (64) On comparison with other

standard therapies (thermal or sclerosant with or without epine-

phrine) clips were less effective at initial hemostasis than thermal

therapy (heater probe) (64) but not signi1047297cantly different in other

outcomes such as urther bleeding However these studies were





MEDICAL THERAPY AFTER ENDOSCOPY

Recommendations

20 Afer successul endoscopic hemostasis intravenous PPI therapy

with 80 mg bolus ollowed by 8 mg h continuous inusion or 72 h

should be given to patients who have an ulcer with active bleeding

a non-bleeding visible vessel or an adherent clot (Strong recommen-

dation high-quality evidence) (Figure 1 )

21 Patients with ulcers that have 1047298at pigmented spots or clean

bases can receive standard PPI therapy (eg oral PPI once-daily)

(Strong recommendation moderate-quality evidence)

Summary of evidence Meta-analysis o randomized trials o intra-

venous PPI therapy (80 mg bolus ollowed by 8 mgh continuous

inusion) vs placebono treatment or 72 h afer endoscopic ther-

apy o high-risk stigmata reveals a signi1047297cant reduction in urther

bleeding (RR = 040 028ndash059 NN = 12) surgery (RR = 043 024ndash

076 NN = 28) and mortality (RR = 041 020ndash084 NN = 45) (64)

In a recent large randomized trial o bolus ollowed by con-

tinuous inusion PPI vs placebo afer successul endoscopichemostasis subgroup analysis o patients with oozing bleeding

showed a very low rebleeding rate with placebo (8163 (49))

(65) Te results o this subgroup analysis suggest that intensive

PPI therapy may not be needed or oozing bleeding without

other SRH

Meta-analysis o trials o intermittent oral or intravenous PPI vs

placebono therapy reveals a signi1047297cant reduction in urther bleed-

ing (RR = 053 035ndash078) but no signi1047297cant difference in surgery

urgent intervention or mortality Meta-analysis o 1047297ve ully pub-

lished randomized trials that compare bolus ollowed by continuous

inusion PPI vs intermittent PPI therapy afer endoscopic therapy

or high-risk stigmata reveals an absolute risk reduction in urtherbleeding with intermittent PPI o 1 (95 CI minus 3 to 5) (85ndash89)

Most o these trials were relatively small methodologic concerns

have been raised about the single large trial and rates o rebleeding

were very low in all arms o the studies (3ndash14) For these reasons

it is diffi cult to conclude that the two treatments are ldquoequivalentrdquo

Nevertheless these data do suggest that intermittent PPI therapy

may suffi ce afer endoscopic therapy or high-risk stigmata

Rates o serious rebleeding with lower risk stigmata (clean base

1047298at pigmented spot) are low (45) and thus standard antisecretory

therapy to heal the ulcer is all that is recommended in patients with

these 1047297ndings

REPEAT ENDOSCOPY

Recommendations

22 Routine second-look endoscopy in which repeat endoscopy is per-

ormed 24 h afer initial endoscopic hemostatic therapy is not recom-

mended (Conditional recommendation moderate-quality evidence)

23 Repeat endoscopy should be perormed in patients with clini-

cal evidence o recurrent bleeding and hemostatic therapy should

be applied in those with higher risk stigmata o hemorrhage (Strong

recommendation high-quality evidence)

24 I urther bleeding occurs afer a second endoscopic therapeutic

session surgery or interventional radiology with transcathether

heterogeneous with one showing clips to be signi1047297cantly better

and two others indicating clips were signi1047297cantly worse than the

comparators in their effect on urther bleeding Tus more data

are needed on the role o clips alone in the acute management o

UGIB Variables to consider in assessing the heterogeneous study

results include variation among different endoscopists and among

different types o clips Newer clips in current use are easier to

apply and vary in size rigidity depth o attachment and duration

o retention (7273) however they have not been well studied in

randomized trials Clips also have the theoretical bene1047297t o not

inducing tissue injury unlike thermal therapies and sclerosantsmdash

and thereore may be preerred in patients on antithrombotic ther-

apy and those undergoing retreatment or rebleeding

Despite showing effi cacy in randomized trials laser mono-

polar electrocoagulation argon plasma coagulation and injec-

tion o thrombin or 1047297brin glue are not recommended as 1047297rst-line

therapies due to less robust evidence potential or slightly

higher risk o adverse effects availability ease o use andor

cost (64)

echniques for endoscopic hemostatic therapy Endoscopic hemo-

static modalities are generally applied to the bleeding site to halt

bleeding and in the immediate area o the SRH in the ulcer base with

the intent to close or obliterate the underlying vessel and prevent

rebleeding Te technique used to treat adherent clots in the two

studies reporting bene1047297t o endoscopic therapy was epinephrine

injection into all our quadrants o the ulcer ollowed by mechani-

cal clot removal (eg snare manipulation with orceps probe or

tip o endoscope) and application o thermal therapy (6166)

Dilute (110000 or 120000 in saline) epinephrine is gener-

ally injected in 05ndash2 ml aliquots in and around the stigmatao hemorrhage in the ulcer base Although large volumes o

epinephrine (eg 30ndash45 ml) are reported to be more effective as

monotherapy (74ndash76) no studies have documented the optimal

volume when used in combination with other modalities We

recommend injection until active bleeding slows or stops or or

non-bleeding stigmata in all our quadrants next to the SRH in

the ulcer base

Absolute alcohol is generally administered in 01ndash02 ml

aliquots with a limitation o 1ndash2 ml (77) due to the concern or

tissue injury with higher volumes Five percent ethanolamine is

administered in 05ndash10 ml aliquots widely variable total volumes

o 05ndash14 ml have been reported in randomized trials or ulcer

bleeding (78ndash80)Bipolar electrocoagulation should be perormed with the

endoscope tip as close as possible to the bleeding ulcer the large

(32 mm) probe should be applied en ace or at the least possible

angulation with 1047297rmmaximal pressure (8182) A setting o ~15 W

and 8ndash10 s applications are recommended (818384) Multiple

applications should be applied in the ulcer base on and around the

SRH until bleeding has stopped the vessel is 1047298attened and the

base is whitened Recommendations or the heater probe are iden-

tical with a setting o 30 J being used

Clips should be placed over the bleeding site and on either side

o the SRH in an attempt to seal the underlying artery




54 Laine and Jensen

arterial embolization is generally employed (Conditional recom-


Summary of evidence Second-look endoscopy is generally

de1047297ned as routine repeat endoscopy within 24 h afer initial

endoscopy and hemostatic therapy Repeat endoscopic hemo-

static therapy is typically given to patients with higher risk SRH

A meta-analysis o randomized trials assessing second-look

endoscopy reported a small but signi1047297cant reduction in rebleed-

ing in patients undergoing second-look endoscopy (absolute risk

reduction = 62 (13ndash111 NN = 16)) with no signi1047297cant

bene1047297t in reducing surgery or death (90) A subsequent meta-

analysis ound no signi1047297cant bene1047297t when hemostatic therapy was

epinephrine injection or 1047297brin glue injection but did identiy a

signi1047297cant difference in rebleeding or the two randomized trials

employing thermal therapy (RR = 029 011ndash073) (91)

However these studies were done beore the currently accepted

practice o adding intensive PPI therapy afer endoscopic therapy

which has been shown to reduce urther bleeding In a randomizedtrial o single endoscopy plus high-dose intravenous PPI vs rou-

tine second-look endoscopy without PPI rebleeding occurred in

82 vs 87 (RR = 11 04ndash27) (91)

Te expense o second-look endoscopy also must be consid-

ered A large number o unnecessary endoscopies will be per-

ormed since most patients do not have recurrent bleeding In

addition second-look endoscopies do not prevent urther bleed-

ing in all patients and repeat endoscopic therapy is successul in

most patients with rebleeding (92) An economic analysis suggests

that intravenous PPI therapy would be the dominant strategy as

compared with second-look endoscopy i the PPI therapy reduced

rebleeding to 9 or i it cost $10 per day (93) Recent randomizedtrials report rebleeding rates lt 9 (4991) in patients with high-

risk ulcer bleeding treated with endoscopic and PPI therapy Fur-

thermore intensive PPI therapy is considered as standard therapy

afer endoscopic therapy o high-risk SRH (as discussed above)

and would be employed even i second-look endoscopy is done

I a population at very high risk o recurrent bleeding afer

endoscopic hemostasis could be identi1047297ed this group potentially

could derive bene1047297t rom second-look endoscopy Although

several characteristics are reported to be associated with an

increased risk o bleeding afer hemostatic therapy no grading

system has been validated to reliably identiy a very high-risk

population (44)

Repeat endoscopy with endoscopic therapy is appropriate inpatients with clinical evidence o rebleeding A randomized trial

comparing endoscopic therapy vs surgery or recurrent bleeding

afer endoscopic hemostatic therapy revealed that 73 o patients

with recurrent bleeding can be successully treated with repeat

endoscopic therapy and avoid the need or surgery with a lower

rate o complications than those treated with surgery (92) I urther

bleeding occurs afer the second endoscopic treatment surgery

or interventional radiology (transcatheter arterial embolization)

is reported to be successul in achieving hemostasis A recent

review o case series o angiographic embolization in patients with

UGIB ailing endoscopic and medical therapy revealed a technical

success rate gt 90 and a rebleeding rate o 33 which was widely

variable across studies (9ndash66) (94)

HOSPITALIZATION FOR PATIENTS WITH UGIB

Recommendations

25 Patients with high-risk stigmata (active bleeding visible vessels

clots) should generally be hospitalized or 3 days assuming no re-

bleeding and no other reason or hospitalization Tey may be ed

clear liquids soon afer endoscopy (Conditional recommendation

low-quality evidence)

26 Patients with clean-based ulcers may receive a regular diet and be

discharged afer endoscopy assuming they are hemodynamically sta-

ble their hemoglobin is stable they have no other medical problems

and they have a residence where they can be observed by a responsi-

ble adult (Strong recommendation moderate-quality evidence)

Summary of evidence Clear liquid diet can be provided afer

endoscopic therapy Tis recommendation is based on theact that patients with recurrent bleeding may have to undergo

urgent interventions such as endoscopy interventional radiol-

ogy or surgery Clear liquids allow sedation or anesthesia to be

administered within 2 h afer the last ingestion (95) Tus we sug-

gest clear liquid diet or ~2 days in patients who are at higher risk

or rebleeding However given the excellent results obtained with

current endoscopic and medical therapy some investigators have

raised the possibility o early reeeding in higher risk patients A

randomized trial o normal diet vs nothing by mouth or 24 h

afer endoscopic therapy or oozing or non-bleeding visible ves-

sels ound no signi1047297cant difference in rebleeding (2 vs 6) (96)

Tis trial may not simulate standard practice however becausesecond-look endoscopy with retreatment was perormed at 24 h

With a low risk o recurrent bleeding regular diet may be insti-

tuted A randomized trial o patients with lower risk lesions (eg

Mallory-Weiss tears ulcers with clean base or 1047298at pigmented

spots) revealed no signi1047297cant differences in outcomes with imme-

diate reeeding o regular diet vs delayed reeeding (clear liquids at

36 h and regular diet at 48 h) (97) Although patients with 1047298at spots

in this trial had similar outcomes with immediate reeeding the

8 rebleeding rate and 5 rate o urgent intervention may argue

or clear liquid diet in these patients or 1ndash2 days Data to guide the

duration o hospitalization or patients with 1047298at pigmented spots

are lacking

Several trials have demonstrated that patients with UGIB whohave low-risk eatures may be discharged on the 1047297rst hospital day

(or worked up and discharged as an outpatient) without negative

consequences (93398) Criteria vary across studies but generally

include low-risk clinical eatures (eg stable vital signs and hemo-

globin no serious comorbidities) low-risk endoscopic eatures

(eg clean-based ulcer erosive disease Mallory-Weiss tear) and

satisactory homesocial support

Other patients with higher risk stigmata (active bleeding visible

vessel and clot) generally remain in the hospital or 3 days assum-

ing no rebleeding or other medical issues Tis is based primarily

on older studies suggesting that recurrent bleeding almost always





Summary of evidence Patients with bleeding ulcers have an

unacceptably high rate o recurrent bleeding i no strategy is

employed to reduce this risk For example in patients with du-

odenal ulcer bleeding (H pylori not assessed no NSAID use)

ollowed in a double-blind trial afer ulcer healing bleeding

recurred within 1 year in nearly 40 (104) In a systematic review o

randomized trials o patients with H pylori -associated bleeding

ulcers (105) the rate o recurrent bleeding in studies with 12-month

ollow-up was 26 (106ndash109) In H pylori -positive NSAID users

with bleeding ulcers ollowed or 6 months afer ulcer healing

recurrent bleeding ulcers occurred with resumption o NSAIDs

in 19 o those given only H pylori therapy (110) while in

H pylori -positive low-dose aspirin users who presented with

ulcer complications and were ollowed or a median o 12 months

afer ulcer healing and H pylori eradication recurrent bleeding

ulcers occurred with resumption o low-dose aspirin in 15 (111)

Finally in a prospective cohort o patients with idiopathic bleed-

ing ulcers (H pylori negative no NSAID use) ollowed or 7 years

the incidence o recurrent ulcer bleeding was 42 (112)

H pylori ulcers

Biopsy-based H pylori testing is recommended by ACG H pylori

guidelines in patients presenting with a bleeding ulcer (113)

Because some studies suggest sensitivity may be decreased with

acute UGIB con1047297rmation o a negative test with a subsequent non-

endoscopic test has also been recommended (113114) However i

histological examination o the biopsy specimens shows no mucosal

mononuclear cell in1047297ltrate the predictive value or absence o

H pylori approaches 100 while a neutrophilic in1047297ltrate has gt 95

positive predictive value or H pylori inection (115)

A meta-analysis o randomized trials showed that H pylori eradication therapy or prevention o recurrent ulcer bleeding is

signi1047297cantly more effective than short-term antisecretory therapy

alone (rebleeding 45 vs 237 OR = 018 010ndash035) (105)

Furthermore H pylori eradication was also more effective

than long-term maintenance antisecretory therapy with PPI or

histamine-2 receptor antagonist (H2RA) (although most patients

received H2RA 16 vs 56 OR = 024 009ndash067) (105) A sys-

tematic review o studies assessing rebleeding in patients with

documented H pylori eradication revealed a 13 incidence o

rebleeding over mean ollow-up periods o 11ndash53 months (105)

(~ge 95) occurred within 3 days (4399ndash101) More recent results

o randomized trials suggest that a substantial minority o patients

may have recurrent bleeding afer 3 daysmdashmost ofen occurring

within 7 days (49102103) For example in a recent large rand-

omized trial o patients with higher risk bleeding ulcers treated

with endoscopic therapy 24 o the 82 patients with rebleeding in

the 30-day study rebled beyond 3 days with equal proportions in

the group receiving continuous inusion PPI and those receiving

placebo afer endoscopic therapy (49) Six percent o rebleeding

occurred afer 7 days (49)

Although patients should be educated about symptoms o UGIB

and the need to return to hospital i these symptoms develop we do

not recommend hospital stays be routinely extended beyond 3 days

in patients without urther bleeding or other medical problems

LONG-TERM PREVENTION OF RECURRENT

BLEEDING ULCERS

Recommendations 27 Patients with H pylori-associated bleeding ulcers should receive

H pylori therapy Afer documentation o eradication maintenance

antisecretory therapy is not needed unless the patient also requires

non-steroidal anti-in1047298ammatory drugs (NSAIDs) or antithrom-

botics (Strong recommendation high-quality evidence) (Figure 2 )

28 In patients with NSAID-associated bleeding ulcers the need or

NSAIDs should be careully assessed and NSAIDs should not be

resumed i possible In patients who must resume NSAIDs a COX-

2-selective NSAID at the lowest effective dose plus daily PPI is

recommended (Strong recommendation high-quality evidence)

29 In patients with low-dose aspirin-associated bleeding ulcers

the need or aspirin should be assessed I given or secondary prevention (ie established cardiovascular disease) then aspirin

should be resumed as soon as possible afer bleeding ceases in

most patients ideally within 1ndash3 days and certainly within 7 days

Long-term daily PPI therapy should also be provided I given or

primary prevention (ie no established cardiovascular disease)

antiplatelet therapy likely should not be resumed in most patients

(Conditional recommendation moderate-quality evidence)

30 In patients with idiopathic (non-H pylori non-NSAID) ulcers

long-term antiulcer therapy (eg daily PPI) is recommended (Con-

ditional recommendation low-quality evidence)

H pylori

H pylori therapy

Document curestop PPIH2RA

NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention

Do not resumeaspirin in most

patients

Secondary CV

prevention

Resume aspirin soon afterhemostasis (eg 1ndash7 days)

in most patients

and start PPI

Idiopathic

Maintenance PPI

Figure 2 Recommended management to prevent recurrent ulcer bleeding based on etiology of ulcer bleeding CV cardiovascular H2RA histamine-2

receptor antagonist NSAID non-steroidal anti-inflammatory drug PPI proton pump inhibitor




56 Laine and Jensen

Because patients with H pylori ulcers have such low rebleeding

rates i they have eradication o the inection it is important to

document cure o the inection at ge 1 month ollowing the end o

H pylori therapy Endoscopic biopsy can be done i patients are

undergoing repeat endoscopy or another reason (eg to docu-

ment gastric ulcer healing) but a urea breath test or stool antigen

test should be done i endoscopy is not needed (113) Antibody

testing should not be employed since it remains positive in most

patients afer successul therapy (116) PPIs can cause alsely nega-

tive H pylori testing in approximately one third o cases (117118)

so PPIs should be discontinued 2 weeks beore testing to ensure

optimal sensitivity (118) Some practitioners may use an H2RA

during this period to decrease risk o recurrent ulcers in case

H pylori therapy was not successul

NSAID ulcers

Randomized trials in NSAID users show that co-therapy with mis-

oprostol PPIs and double-dose H2RAs or use o COX-2-selective

inhibitors decrease endoscopic ulcers in patients taking NSAIDs(119120) and that misoprostol and COX-2-selective NSAIDs

also decrease complicated ulcers in arthritis patients (120121)

Although these trials suggest that the agents studied may be ben-

e1047297cial in patients who presented with a bleeding ulcer they do not

speci1047297cally address management o these high-risk patients

Several randomized trials rom Hong Kong have studied pre-

vention o recurrent bleeding in NSAID users who presented with

bleeding ulcers In patients who were restarted on NSAID afer

ulcer healing maintenance PPI therapy had a signi1047297cantly lower

risk o recurrent ulcer bleeding at 6 months as compared with

H pylori therapy only (44 vs 188 NN = 7) (110) In a ollow-

up study celecoxib was compared with dicloenac plus PPI aferulcer healing in patients who were H pylori negative or had suc-

cessul H pylori therapy (122) Te rates o recurrent ulcer bleed-

ing at 6 months were 49 with celecoxib and 64 or dicloenac

plus PPI recurrent ulcers were seen at 6-month endoscopy in 19

and 26 o patients (123) Because rates o recurrent ulcer bleed-

ing were relatively high with either protective strategy a subse-

quent 12-month double-blind study o similar design compared

celecoxib plus twice-daily PPI vs celecoxib plus placebo (124)

Recurrent ulcer bleeding occurred in 0 vs 89 (NN = 12) Tus

patients with a bleeding ulcer while on NSAIDs who must remain

on NSAIDs should receive a COX-2-selective NSAID at the lowest

effective dose plus PPI therapy

Low-dose aspirin ulcers

Randomized trials in low-dose aspirin users show that PPIs and

standard dose H2RAs reduce endoscopic ulcers (125ndash127) and

that PPIs reduce UGIB in patients taking low-dose aspirin plus

clopidogrel (128)

In a study o H pylori -positive low-dose aspirin users with

bleeding ulcers the rates o recurrent ulcer bleeding at 6 months

afer resuming low-dose aspirin were 09 with PPI and 19

with H pylori therapy (110) Although no placebo group was

included this trial raised the possibility that H pylori eradication

alone may reduce recurrent ulcer bleeding with low-dose aspirin

A subsequent trial perormed in H pylori -positive low-dose aspi-

rin users with ulcer complications showed that afer H pylori

eradication and ulcer healing PPI therapy had signi1047297cantly less

recurrent ulcer bleeding than placebo at a median o 12 months

(16 vs 148 NN = 8) (111) Tus in patients with bleeding

ulcers who require continued antiplatelet therapy once-daily PPI

should be given

Te need or antiplatelet therapy should be reviewed in patients

who have ulcer bleeding while taking low-dose aspirin In patients

taking aspirin or primary prophylaxis (no overt cardiovascular dis-

ease) the bene1047297t o low-dose aspirin is relatively small meta-analy-

sis o randomized trials reveals an annual absolute risk reduction o

007 (NN = 1429) (129) Primary prevention is recommended

only in patients at higher risk or cardiovascular events based on

risk assessment tools In patients hospitalized with ulcer bleeding

the risk o subsequent bleeding likely outweighs the cardiovascular

bene1047297t in many or most patients on primary prophylaxis

In contrast the bene1047297t o low-dose aspirin or secondary proph-

ylaxis in patients with established cardiovascular disease is muchlarger (annual absolute risk reduction o 149 (NN = 68)) (129)

and ailure to resume low-dose aspirin afer ulcer bleeding is

associated with an increased mortality (130) A randomized trial

in low-dose aspirin users with established cardiovascular disease

who presented with a bleeding ulcer showed that resumption o

low-dose aspirin vs placebo afer endoscopic hemostasis and ini-

tiation o PPI therapy was associated with no signi1047297cant increase

in recurrent ulcer bleeding at 1 month (103 vs 54) but a signi1047297-

cant decrease in mortality at 1 month and 2 months (13 vs 129)

(130) Tus it is important to resume antiplatelet therapy along

with PPI co-therapy as early as possible in patients with estab-

lished cardiovascular diseaseTe timing o resumption o aspirin is not clear and data are pri-

marily based on observational studies A systematic review ound

that thrombotic events in patients with established cardiovascular

disease occurred at a mean o 107 days afer aspirin withdrawal

(131) while another review o patients on secondary prevention

stopping aspirin perioperatively reported the mean interval afer

discontinuation or acute cerebral events was 143 days and or

acute coronary syndrome was 85 days (132) Recent joint consen-

sus recommendations rom US cardiology and GI organizations

stated that ldquoreintroduction o antiplatelet therapy in high-cardio-

vascular-risk patients is reasonable in those who remain ree o

rebleeding afer 3ndash7 daysrdquo (133) while the study rom Sung et al

(130) indicated a bene1047297t o resumption o low-dose aspirin imme-diately afer endoscopic hemostasis in patients with high-risk stig-

mata Tus the bene1047297t-risk ratio o aspirin resumption must be

careully considered jointly by gastroenterologists cardiologists

neurologists and patients on a case-by-case basis However early

resumption o antiplatelet therapy within 1ndash3 days afer hemosta-

sis and certainly within 7 days will be appropriate in most patients

with established cardiovascular disease

Idiopathic (non-H pylori non-NSAID) ulcers

Patients with idiopathic bleeding ulcers have a high rate o

recurrence when ollowed without protective co-therapy (112)





REFERENCES1 Guyatt GH Oxman AD Vist GE et al GRADE an emerging consensus

on rating quality o evidence and strength o recommendations BMJ2008336924ndash6

2 Cocchi MN Kimlin E Walsh M et al Identi1047297cation and resuscitation o thetrauma patient in shock Emerg Med Clin N Am 200725623ndash42

3 Hebert PC Wells G Blajchman MA et al A multicenter randomized con-

trolled clinical trial o transusion requirements in critical care ransusionRequirements in Critical Care Investigators Canadian Critical Care rialsGroup N Engl J Med 1999340409ndash17

4 Colomo A Hernaacutendez-Gea V Muntildeiz-Diacuteaz E et al ransusion strategiesin patients with cirrhosis and acute gastrointestinal bleeding Hepatology200848413A

5 Blair SD Janvrin SB McCollum CN et al Effect o early blood transusionon gastrointestinal haemorrhage Br J Surg 198673783ndash5

6 Wu WC Rathore SS Wang Y et al Blood transusion in elderly patientswith acute myocardial inarction N Engl J Med 20013451230ndash6

7 Rockall A Logan RFA Devlin HB et al Risk assessment afer acute uppergastrointestinal haemorrhage Gut 199638316ndash21

8 Blatchord O Murray WR Blatchord M A risk score to predict needor treatment or upper gastrointestinal haemorrhage Lancet 2000356 1318ndash21

9 Stanley AJ Ashley D Dalton HR et al Outpatient management o patientswith low-risk upper-gastrointestinal haemorrhage multicentre validation

and prospective evaluation Lancet 200937342ndash710 Chen IC Hung MS Chiu F et al Risk scoring systems to predict need or

clinical intervention or patients with nonvariceal upper gastrointestinalbleeding Am J Emerg Med 200725774ndash9

11 Pang SH Ching JYL Lau JYW et al Comparing the Blatchord andpre-endoscopic Rockall score in predicting the need or endoscopictherapy in patients with upper GI hemorrhage Gastrointest Endosc2010711134ndash40

12 Barkun AN Bardou M Martel M et al Prokinetics in acute upper GI bleed-ing a meta-analysis Gastrointest Endosc 2010721138ndash45

13 Carbonell N Pauwels A Seraty L et al Erythromycin inusion prior toendoscopy or acute upper gastrointestinal bleeding a randomized control-led double-blind trial Am J Gastroenterol 20061011211ndash5

14 Coffi n B Pocard M Panis Y et al Erythromycin improves the quality oEGD in patients with acute upper GI bleeding a randomized controlledstudy Gastrointest Endosc 200256174ndash9

15 Frossard JL Spahr L Queneau PE et al Erythromycin intravenous bolusinusion in acute upper gastrointestinal bleeding a randomized controlleddouble-blind trial Gastroenterology 200212317ndash23

16 Altrai I Handoo FA Aljumah A et al Effect o erythromycin beoreendoscopy in patients presenting with variceal bleeding a prospectiverandomized double-blind placebo-controlled trial Gastrointest Endosc201173245ndash50

17 Pateron D Vicaut E Debuc E et al Erythromycin inusion or gastric lavageor upper gastrointestinal bleeding a multicenter randomized controlledtrial Ann Emerg Med 201157582ndash9

18 Sreedharan A Martin J Leontiadis GI et al Proton pump inhibitor treat-ment initiated prior to endoscopic diagnosis in upper gastrointestinalbleeding Cochrane Database Syst Rev 2010 (7) CD005415

19 Lau JY Leung WK Wu JCY et al Omeprazole beore endoscopy in patientswith gastrointestinal bleeding N Engl J Med 20073561631ndash40

20 Leontiadis GI Sharma VK Howden CW Proton pump inhibitor therapyor peptic ulcer bleeding Cochrane collaboration meta-analysis o rand-

omized controlled trials Mayo Clin Proc 200782286ndash9621 Silverstein FE Gilbert DA edesco FJ et al Te national ASGE survey on

upper gastrointestinal bleeding II Clinical prognostic actors GastrointestEndosc 19812780ndash93

22 Aljebreen AM Fallone CA Barkun AN Nasogastric aspirate predictshigh-risk endoscopic lesions in patients with acute upper-GI bleedingGastrointest Endosc 200459172ndash8

23 Gilbert DA Silverstein FE edesco FJ et al Te national ASGE survey onupper gastrointestinal bleedingmdashIII Endoscopy in upper gastrointestinalbleeding Gastrointest Endosc 19812792ndash102

24 Ahmad A Bruno JM Boynton R et al Nasogastric aspirates requently leadto erroneous results and delay o therapy in patients with suspected UGIbleeding Gastroinest Endosc 200459P163

25 Cuellar RE Gavaler JS Alexander JA et al Gastrointestinal tracthemorrhage Te value o a nasogastric aspirate Arch Intern Med 1990 1501381ndash4

Surreptitious NSAID use undoubtedly accounts or some o

these ulcers Although no randomized trials have assessed the

bene1047297t o medical co-therapy in this population antiulcer therapy

seems likely to reduce recurrent idiopathic ulcers and will also

be effective at reducing recurrent ulcers in those surreptitiously

using NSAIDs

CONCLUSION

Management o the patient presenting with overt bleeding

proceeds in a step-wise manner Te 1047297rst step is assessment o

hemodynamic status and initiation o resuscitative measures as

needed Patients are risk strati1047297ed based on clinical eatures such

as hemodynamic status comorbidities age and initial labora-

tory tests Most patients should receive an upper endoscopy

within 24 h or less and endoscopic eatures o the ulcer assist in

directing urther management Tose with high-risk 1047297ndings o

active bleeding or non-bleeding visible vessel should receive

endoscopic therapy and those with an adherent clot may receiveendoscopic therapy these patients should then receive intrave-

nous PPI therapy with a bolus ollowed by continuous inusion

Tose with 1047298at spots or clean-based ulcers do not require endo-

scopic therapy or intensive intravenous PPI therapy Recur-

rent ulcer bleeding afer endoscopic therapy should be treated

with a second endoscopic treatment but i bleeding still persists

or recurs treatment with surgery or interventional radiology is

undertaken

Prevention o recurrent bleeding is based on the presumed

etiology o the bleeding ulcer H pylori should be eradicated

i present and afer cure is documented no urther therapy is

needed NSAIDs should be stopped i they must be continueda low-dose o a COX-2-selective NSAID plus a PPI should be

used Patients with established cardiovascular disease who require

aspirin or other antiplatelet agents should start PPI therapy and

generally have antiplatelet therapy reinstituted as soon as possible

afer bleeding ceases (ideally within 1ndash3 days and certainly within

7 days) Tose with idiopathic ulcers should receive long-term

antiulcer therapy

CONFLICT OF INTEREST

Guarantor of the article Loren Laine MD

Speci1047297c author contributions L Laine planning and conducting

review analysisinterpretation o data drafing and revision o the

manuscript He approved 1047297nal draf submitted D Jensen planningand conducting review analysisinterpretation o data critical

review and revision o the manuscript He approved 1047297nal draf

submitted

Financial support None

Potential competing interests L Laine has served as a consultant

or AstraZeneca Eisai P1047297zer Horizon and Logical Terapeutics

and has served on Data Saety Monitoring Boards or Bayer BMS

and Merck D Jensen is a consultant or AstraZeneca Boston

Scienti1047297c Merck and US Endoscopy D Jensen has received

research grants rom Boston Scienti1047297c Pentax Olympus US

Endoscopy and Vascular echnology Inc




58 Laine and Jensen

26 Jensen DM Machicado GA Diagnosis and treatment o severe hema-tochezia Te role o urgent colonoscopy afer purge Gastroenterology1988951569ndash74

27 Laine L Shah A Randomized trial o urgent vs elective colonoscopyin patients hospitalized with lower GI bleeding Am J Gastroenterol20101052636ndash41

28 Lin HJ Kun W Perng CL et al Early or delayed endoscopy or patients withpeptic ulcer bleeding a prospective randomized study J Clin Gastroenterol199622267ndash71

29 Lee SD Kearney KJ A randomized controlled trial o gastric lavage prior toendoscopy or acute upper gastrointestinal bleeding J Clin Gastroenterol200438861ndash5

30 Kodali VP Petersen B Miller CA et al A new jumbo-channel therapeuticgastroscope or acute upper gastrointestinal bleeding Gastrointest Endosc199745409ndash11

31 Sedarat A Jensen D Ohning G et al De1047297nitive endoscopic diagnosis andhemostasis when clots obscure the bleeding site in severe UGI hemorrhageprevalence techniques amp results Am J Gastroenterol 2011106(Suppl 2) S541

32 Ponsky JL Hoffman M Swayngim DS Saline irrigation in gastric hemor-rhage the effect o temperature J Surg Res 198028204ndash5

33 Spiegel BM Vakil NB Oman JJ Endoscopy or acute nonvariceal uppergastrointestinal tract hemorrhage is sooner better A systematic reviewArch Intern Med 20011611393ndash404

34 soi KKF Ma KW Sung JJY Endoscopy or upper gastrointestinal

bleeding How urgent is it Nat Rev Gastroenterol Hepatol 20096 463ndash9

35 Cooper GS Chak A Way LE Early endoscopy in upper gastrointestinalhemorrhage associations with recurrent bleeding surgery and length ohospital stay Gastrointest Endosc 199949145ndash52

36 Cooper GS Chak A Connors AF Jr et al Te effectiveness o early endos-copy or upper gastrointestinal hemorrhage a community based analysisMed Care 199836462ndash74

37 Lee JG urnipseed S Romano C et al Endoscopy-based triage signi1047297cantlyreduces hospitalization rates and costs o treating upper GI bleeding arandomized controlled trial Gastrointest Endosc 199950755ndash61

38 Bjorkman DJ Zaman A Fennerty MB et al Urgent vs elective endoscopyor acute non-variceal upper-Gi bleeding an effectiveness study Gastroin-test Endosc 2004601ndash8

39 Lim LG Ho KY Chan YH et al Urgent endoscopy is associated with lowermortality in high-risk but hot low-risk nonvariceal upper gastrointestinalbleeding Endoscopy 201143300ndash6

40 Yen D Hu S Chen L et al Arterial oxygen desaturation during emergentnonsedated upper gastrointestinal endoscopy in the emergency depart-ment Am J Emerg Med 199715644ndash7

41 Swain CP Storey DW Bown SG et al Nature o the bleeding vessel in recur-rently bleeding gastric ulcers Gastroenterology 198690595ndash608

42 Branicki FJ Coleman SY Fok PJ et al Bleeding peptic ulcer a prospec-tive evaluation o risk actors or rebleeding and mortality World J Surg199014262ndash70

43 Lin HJ Perng CL Lee FY et al Clinical courses and predictors or rebleed-ing in patients with peptic ulcers and non-bleeding visible vessels Gut1994351389ndash93

44 Elmunzer BJ Young SD Inadomi JM et al Systematic review o the predic-tors o recurrent hemorrhage afer endoscopic hemostatic therapy orbleeding peptic ulcers Am J Gastroenterol 20081032625ndash32

45 Laine L Peterson WL Bleeding peptic ulcer N Engl J Med 1994331717ndash27

46 Savides S Jensen DM GI bleeding In Feldman M Friedman LS BrandtLJ (eds) Sleisenger and Fordtranrsquos Gastrointestinal and Liver DiseasePathophysiologyDiagnosisManagement 8th edn Saunders ElsevierPhiladelphia 2010 pp 285ndash322

47 Swain CP Kalabakas A Rampton DS et al A prospective study o theincidence and signi1047297cance o stigmata o recent hemorrhage in ulcerpatients without clinical evidence o recent bleeding Gastroenterology1991100A171

48 Enestvedt BK Gralnek IM Mattek N et al An evaluation o endoscopicindications and 1047297ndings related to nonvariceal upper-GI hemorrhage in alarge multicenter consortium Gastrointest Endosc 200867422ndash9

49 Sung JJ Barkun A Kuipers EJ et al Intravenous esomeprazole or preven-tion o recurrent peptic ulcer bleeding a randomized trial Ann Intern Med200950455ndash64

50 Chung SCS Leung JWC Steele RJC et al Endoscopic injection oadrenaline or actively bleeding ulcers a randomized trial Br Med J19882961631ndash3

51 Chang-Chien CS Wu CS Chen PC et al Different implications o stig-mata o recent hemorrhage in gastric and duodenal ulcers Dig Dis Sci198833400ndash4

52 Kovacs OG Jensen DM Recent advances in the endoscopic diagnosis andtherapy o upper gastrointestinal small intestinal and colonic bleedingMed Clin N Am 2002861319ndash56

53 ekant Y Goh P Alexander D et al Combination therapy using adrenalineand heater probe to reduce rebleeding in patients with peptic ulcer haemor-rhage a prospective randomized trial Br J Surg 199582223ndash6

54 Fullarton G Birnie G Macdonald A et al Controlled trial o heater probetreatment in bleeding peptic ulcers Br J Surg 198976541ndash4

55 Pascu O Draghici A Acalovchi I Te effect o endoscopic hemostasis withalcohol on the mortality rate o nonvariceal upper gastrointestinal hemor-rhage A randomized prospective study Endoscopy 19892153ndash5

56 Freitas D Donato A Monteiro JG Controlled trial o liquid monopo-lar electrocoagulation in bleeding peptic ulcers Am J Gastroenterol198580853ndash7

57 Wara P Endoscopic prediction o major rebleeding-a prospective study ostigmata o hemorrhage in bleeding ulcer Gastroenterology 1985881209ndash14

58 Fullarton GM Murray WR Prediction o rebleeding in peptic ulcers by visual stigmata and endoscopic Doppler ultrasound criteria Endoscopy19902268ndash71

59 Laine L Friedman M Cohen H Lack o uniormity in evaluation o

endoscopic prognostic eatures o bleeding ulcers Gastrointest Endosc199440411ndash7

60 Lau JYW Sung JJY Chan ACW et al Stigmata o hemorrhage in bleed-ing peptic ulcers an interobserver agreement study among internationalexperts Gastrointest Endosc 19974633ndash6

61 Jensen D Kovacs Jutabha R et al Randomized trial o medical orendoscopic therapy to prevent recurrent ulcer hemorrhage in patients withadherent clots Gastroenterology 2002123407ndash13

62 Lin JH Wang K Perng KL et al Natural history o bleeding peptic ulcerswith a tightly adherent blood clot a prospective observation GastrointestEndosc 199643470ndash3

63 Laine L Stein C Sharma V A prospective outcome o patients withclot in an ulcer and the effect o irrigation Gastrointest Endosc 199643 107ndash10

64 Laine L McQuaid KR Endoscopic therapy or bleeding ulcers an evi-dence-based approach based on meta-analyses o randomized controlledtrials Clin Gastroenterol Hepatol 2009733ndash47

65 Jensen DM Ahlbom H Eklund S et al Rebleeding risk or oozing pepticulcer bleeding (PUB) in a large international studymdasha reassessment basedupon a multivariate analysis Gastrointest Endosc 201071AB117

66 Bleau B Gostout C Sherman K et al Recurrent bleeding rom peptic ulcerassociated with adherent clot a randomized study comparing endoscopictreatment with medical therapy Gastrointest Endosc 2002561ndash6

67 Sung J Chan F Lau J et al Te effect o endoscopic therapy in patientsreceiving omeprazole or bleeding ulcers with nonbleeding visible vessels oradherent clots a randomized comparison Ann Intern Med 2003139237ndash43

68 Laine L Spiegel B Rostom A et al Methodology or randomized trials opatients with nonvariceal upper gastrointestinal bleeding recommenda-tions rom an international consensus conerence Am J Gastroenterol2010105540ndash50

69 Bianco M Rotondano G Marmo R et al Combined epinephrine andbipolar probe coagulation vs bipolar probe coagulation alone or bleed-

ing peptic ulcer a randomized controlled trial Gastrointest Endosc200460910ndash5

70 Lin H seng G Perng C et al Comparison o adrenaline injection andbipolar electrocoagulation or the arrest o peptic ulcer bleeding Gut199944715ndash9

71 Church N Dallal H Masson J et al A randomized trial comparing heaterprobe plus thrombin with heater probe plus placebo or bleeding pepticulcer Gastroenterology 2003125396ndash403

72 Jensen DM Machicado GA Hirabayashi K Randomized controlled studyo three different types o hemoclips or hemostasis o bleeding canineacute gastric ulcers Gastrointest Endosc 200664768ndash73

73 Jensen DM Machicado GA Hemoclipping o chronic ulcers a randomizedprospective study o initial deployment success clip retention rates andulcer healing Gastrointest Endosc 200970969ndash75

74 Lin H Hsieh H seng G et al A prospective randomized trial o large- vssmall-volume injection o ephinephrine or peptic ulcer bleeding Gastroin-test Endosc 200255615ndash9





99 Lau JYW Chung SCS Leung JW et al Te evolution o stigmata ohemorrhage in bleeding peptic ulcers as sequential endoscopic studyEndoscopy 199830513ndash8

100 Hsu PI Lin XZ Chan SH et al Bleeding peptic ulcermdashrisk actorsor rebleeding and sequential changes in endoscopic 1047297ndings Gut199435746ndash9

101 Hsu PI Lai KH Lin XZ et al When to discharge patients with bleedingpeptic ulcers a prospective study o residual risk o rebleeding Gastroin-test Endosc 199644382ndash7

102 Jensen D Pace S Soffer E et al Continuous inusion o pantoprazole vsranitidine or prevention o ulcer rebleeding a US multicenter rand-omized double-blind study Am J Gastroenterol 20061011991ndash9

103 Zargar S Javid G Khan B et al Pantoprazole inusion as adjuvanttherapy to endoscopic treatment in patients with peptic ulcer bleed-ing prospective randomized controlled trial J Gastroenterol Hepatol200621716ndash21

104 Jensen DM Cheng S Kovacs OG et al A controlled study o ranitidineor the prevention o recurrent hemorrhage rom duodenal ulcer N Engl JMed 1994330382ndash6

105 Gisbert JP Khorrami S Carballo F et al Meta-analysis Helicobacter pylorieradication therapy vs antisecretory non-eradication therapy or the prevention o recurrent bleeding rom peptic ulcer Aliment Pharmacol Ter200419617ndash29

106 Jaspersen D Koerner Schorr W et al Helicobacter pylori eradication

reduces the risk o rebleeding in ulcer hemorrhage Gastrointest Endosc1995415ndash7

107 Rokkas Karameris A Mavrogeorgis A et al Eradication o Helicobaterpylori reduces the possibility o rebleeding in peptic ulcer disease Gas-trointest Endosc 1995411ndash4

108 Vcev A Horvat D Rubinic M et al Eradication o Helicobacter pylorireduces the possibility o rebleeding in duodenal ulcer disease Acta FamMed Flum 19962159ndash65

109 Bataga S Bratu B Bancu L et al Te treatment in bleeding duodenal ulcerGut 199741 (Suppl 3) A167

110 Chan FKL Chung SCS Suen BY et al Preventing recurrent uppergastrointestinal bleeding in patients with Helicobacter pylori inectionwho are taking low-dose aspirin or naproxen N Engl J Med 2001 344967ndash73

111 Lai KC Lam SK Chu KM et al Lansoprazole or the prevention o recur-rences o ulcer complications rom long-term low-dose aspirin use N EnglJ Med 20023462033ndash8

112 Wong GLH Wong VWS Chan Y et al High incidence o mortality andrecurrent bleeding in patients with Helicobacter pylori-negative idiopathicbleeding ulcers Gastroenterology 2009137525ndash31

113 Chey WD Wong BCY American College o Gastroenterology guidelineon the Management o Helicobacter pylori inection Am J Gastroenterol20071021808ndash25

114 Barkun AN Bardou M Kuipers EJ et al International consensus recom-mendations on the management o patients with nonvariceal uppergastrointestinal bleeding Ann Intern Med 2010152101ndash13

115 Cutler AF Havstad S Ma CK et al Accuracy o invasive and noninva-sive tests to diagnose Helicobacter pylori inection Gastroenterology1995109136ndash41

116 Cutler AF Prasad VM Santagode P Four-year trends in Helicobacterpylori IgG serology ollowing successul eradication Am J Med199810518ndash20

117 Hui WM Lam SK Ho J et al Effect o omeprazole on duodenal ulcer-

associated antral gastritis and Helicobacter pylori Dig Dis Sci199136577ndash82

118 Laine L Estrada R rujillo M et al Te effect o proton pump inhibitortherapy on diagnostic testing or Helicobacter pylori Ann Intern Med1998129547ndash50

119 Rostom A Dube C Wells G et al Prevention o NSAID-induced gastrodu-odenal ulcers Cochrane Database Syst Rev 2002 (4) CD0022962002

120 Rostom A Muir K Dube C et al Te gastrointestinal toxicity o COX-2inhibitors a Cochrane Collaboration Systematic Review Clin Gastroen-terol Hepatol 20075818ndash28

121 Silverstein FE Graham DY Senior JR et al Misoprostol reduces seriousgastrointestinal complications in patients with rheumatoid arthritis receiv-ing nonsteroidal anti-in1047298ammatory drugs A randomized double-blindplacebo-controlled trial Ann Intern Med 1995123241ndash9

122 Chan FK Hung LC Suen BY et al Celecoxib vs dicloenac and ome-prazole in reducing the risk o recurrent ulcer bleeding in patients witharthritis N Engl J Med 20023472104ndash10

75 Park C Lee S Park J et al Optimal injection volume o epinephrine or en-doscopic prevention o recurrent peptic ulcer bleeding Gastrointest Endosc200460875ndash80

76 Liou Lin S Wang H et al Optimal injection volume o epinephrine orendoscopic treatment or peptic ulcer bleeding World J Gastroenterol2006123108ndash13

77 Laine L Multipolar electrocoagulation vs injection therapy in the treat-ment o bleeding peptic ulcers A prospective randomized trial Gastroen-terology 1990991303ndash6

78 Choudari C Rajgopal C Palmer K Comparison o endoscopic injec-tion therapy vs the heater probe in major peptic ulcer haemorrhage Gut1992331159ndash61

79 Choudari C Palmer K Endoscopic injection therapy or bleeding pepticulcer a comparison o adrenaline alone with adrenaline plus ethanolamineoleate Gut 199435608ndash10

80 Moretoacute M Zaballa M Suaacuterez M et al Endoscopic local injection oethanolamine oleate and thrombin as an effective treatment or bleedingduodenal ulcer a controlled trial Gut 199233456ndash9

81 Laine LA Determination o the optimum technique or bipolar electroco-agulation treatment Gastroenterology 1991100107ndash12

82 Morris DL Brearley S Tompson H et al A comparison o the effi cacy anddepth o gastric wall injury with 32- and 23-mm bipolar probes in caninearterial hemorrhage Gastrointest Endosc 198531361ndash3

83 Jensen DM Machicado GA Endoscopic hemostasis o ulcer hemorrhage

with injection thermal or combination methods ech Gastrointest Endosc20057124ndash31

84 Laine L Long GL Bakos GJ et al Optimizing bipolar electrocoagulation orendoscopic hemostasis assessment o actors in1047298uencing energy deliveryand coagulation Gastrointest Endosc 200867502ndash8

85 Hung WK Li VK Chung CK et al Randomized trial comparing pantopra-zole inusion bolus and no treatment on gastric pH and recurrent bleedingin peptic ulcers ANZ J Surg 200777677ndash81

86 Andriulli A Loper1047297do S Focareta R et al High vs low-dose protonpump inhibitors afer endoscopic hemostasis in patients with pepticulcer bleeding a multicentre randomized study Am J Gastroenterol20081033011ndash8

87 Yuumlksel I Ataseven H Koumlkluuml S et al Intermittent vs continuous pantopra-zole inusion in peptic ulcer bleeding a prospective randomized studyDigestion 20087839ndash43

88 Choi KD Kim N Jang IJ et al Optimal dose o intravenous pantoprazolein patients with peptic ulcer bleeding requiring endoscopic hemostasis inKorea J Gastroenterol Hepatol 2009241617ndash24

89 Javid G Zargar SA U-Sai R et al Comparison o po or iv proton pumpinhibitors on 72-h intragastri c pH in bleeding peptic ulcer J Gastroen-terol Hepatol 2009241236ndash43

90 Marmo R Rotondano G Blanco MA et al Outcome o endoscopic treat-ment or peptic ulcer bleeding is a second look necessary A meta-analy-sis Gastrointest Endosc 20035762ndash7

91 soi KKF Chan HCH Chiu PWY et al Second-look endoscopy with ther-mal coagulation or injections or peptic ulcer bleeding A meta-analysisJ Gastroenterol Hepatol 2010258ndash13

92 Lau JY Sung JJ Lam YH et al Endoscopic retreatment compared withsurgery in patients with recurrent bleeding afer initial endoscopic controlo bleeding ulcers N Engl J Med 1999340751ndash6

93 Spiegel BMR Oman JJ Woods K et al Minimizing recurrent peptic ulcerhemorrhage afer endoscopic hemostasis the cost-effectiveness o compet-ing strategies Am J Gastroenterol 20039386ndash97

94 Loffroy R Rao P Ota S et al Embolization o acute nonvariceal uppergastrointestinal hemorrhage resistant to endoscopic treatment resultsand predictors o recurrent bleeding Cardiovasc Intervent Radiol2010331088ndash100

95 Gross JB Bailey PL Connis R et al Practice guidelines or sedationand analgesia by non-anesthesiologists Anesthesiology 200296 1004ndash17

96 Hepworth CC Newton M Barton S et al Randomized controlled trial oearly eeding in patients with bleeding peptic ulcer and a visible vesselGastroenterology 1995108A113

97 Laine L Cohen H Brodhead J et al A prospective evaluation o immedi-ate vs delayed reeeding and the prognostic value o endoscopic eaturesin patients with major upper gastrointestinal tract hemorrhage Gastroen-terology 1992102314ndash6

98 Cipolletta L Bianco MA Rotondano G et al Outpatient management orlow-risk nonvariceal upper GI bleeding a randomized controlled trialGastroinest Endosc 2002551ndash5



60 Laine and Jensen

123 Chan FKL Hung LC Suen BY et al Celecoxib vs dicloenac plusomeprazole in high-risk arthritis patients results o a randomized double-blind trial Gastroenterology 20041271038ndash43

124 Chan FK Wong VW Suen BY et al Combination o a cyclo-oxygenase-2inhibitor and a proton-pump inhibitor or prevention o recurrent ulcerbleeding in patients at very high risk a double-blind randomised trialLancet 20073691621ndash6

125 Yeomans N Lanas A Labenz J et al Effi cacy o esomeprazole (20 mgonce daily) or reducing the risk o gastroduodenal ulcers associatedwith continuous use o low-dose aspirin Am J Gastroenterol 2008 1032465ndash73

126 Scheiman JM Devereaux PJ Herlitz J et al Prevention o peptic ulcerswith escomeprazole in patients at risk o ulcer development treated withlow-dose acetylsalicylic acid a randomized controlled trial (OBERON)Heart 201197797ndash802

127 aha A McCloskey C Prasad R et al Famotidine or the prevention opeptic ulcers and oesophagitis in patients taking low-dose aspirin (FA-MOUS) a phase III randomised double-blind placebo-controlled trialLancet 2009374119ndash25

128 Bhatt DL Cryer BL Contant CF et al Clopidogrel with or without ome-prazole in coronary artery disease N Engl J Med 20103631909ndash17

129 Antithrombotic rialists (A) Collaboration Aspirin in the primaryand secondary prevention o vascular disease collaborative meta-analysiso individual participant data rom randomised trials Lancet 2009 3731849ndash60

130 Sung JJY Lau JWY Ching JYL et al Continuation o low-dose aspirintherapy in peptic ulcer bleeding a randomized trial Ann Intern Med20101521ndash9

131 Biondi-Zoccai GG Lotrionte M Agostoni P et al A systematic review andmeta-analysis on the hazards o discontinuing or not adhering to aspirinamong 50279 patients at risk or coronary artery disease Eur Heart J2006272667ndash74

132 Burger W Chemnitius JM Kneissl GD et al Low-dose aspirin or second-ary cardiovascular prevention-cardiovascular risks afer its perioperativewithdrawal vs bleeding risks with its continuation-review and meta-analysis J Intern Med 2005257399ndash414

133 Abraham NS Hlatky MA Antman EM et al ACCFACGAHA 2010expert consensus document on the concomitant use o proton pumpinhibitors and thienopyridines a ocused update o the ACCFACGAHA2008 expert consensus document on reducing the gastrointestinal riskso antiplatelet therapy and NSAID use Am J Gastroenterol 2010105 2533ndash49




46 Laine and Jensen

Table 1 Summary and strength of recommendations

Initial assessment and risk stratification

1 Hemodynamic status should be assessed immediately upon presentation and resuscitative measures begun as needed (Strong recommendation)

2 Blood transfusions should target hemoglobin ge 7 g dl with higher hemoglobins targeted in patients with clinical evidence of intravascular volume depletion

or comorbidities such as coronary artery disease (Conditional recommendation)

3 Risk assessment should be performed to stratify patients into higher and lower risk categories and may assist in initial decisions such as timing of

endoscopy time of discharge and level of care (Conditional recommendation)

4 Discharge from the emergency department without inpatient endoscopy may be considered in patients with urea nitrogen lt 182 mg dl hemoglobin

ge 130 g dl for men (120 g dl for women) systolic blood pressure ge 110 mm Hg pulse lt 100 beats min and absence of melena syncope cardiac failure

and liver disease as they have lt 1 chance of requiring intervention (Conditional recommendation)

Pre-endoscopic medical therapy

5 Intravenous infusion of erythromycin (250 mg ~30 min before endoscopy) should be considered to improve diagnostic yield and decrease the need for

repeat endoscopy However erythromycin has not consistently been shown to improve clinical outcomes (Conditional recommendation)

6 Pre-endoscopic intravenous PPI (eg 80 mg bolus followed by 8 mg h infusion) may be considered to decrease the proportion of patients who have

higher risk stigmata of hemorrhage at endoscopy and who receive endoscopic therapy However PPIs do not improve clinical outcomes such as further

bleeding surgery or death (Conditional recommendation)

7 If endoscopy will be delayed or cannot be performed intravenous PPI is recommended to reduce further bleeding (Conditional recommendation)

Gastric lavage

8 Nasogastric or orogastric lavage is not required in patients with UGIB for diagnosis prognosis visualization or therapeutic effect (Conditional recommendation)

Timing of endoscopy

9 Patients with UGIB should generally undergo endoscopy within 24 h of admission following resuscitative efforts to optimize hemodynamic parameters and

other medical problems (Conditional recommendation)

10 In patients who are hemodynamically stable and without serious comorbidities endoscopy should be performed as soon as possible in a non-emergent

setting to identify the substantial proportion of patients with low-risk endoscopic findings who can be safely discharged (Conditional recommendation)

11 In patients with higher risk clinical features (eg tachycardia hypotension bloody emesis or nasogastric aspirate in hospital) endoscopy within 12 h may

be considered to potentially improve clinical outcomes (Conditional recommendation)

Endoscopic diagnosis

12 Stigmata of recent hemorrhage should be recorded as they predict risk of further bleeding and guide management decisions The stigmata in descending

risk of further bleeding are active spurting non-bleeding visible vessel active oozing adherent clot flat pigmented spot and clean base (Strong recommendation)

Endoscopic therapy

13 Endoscopic therapy should be provided to patients with active spurting or oozing bleeding or a non-bleeding visible vessel (Strong recommendation)

14 Endoscopic therapy may be considered for patients with an adherent clot resistant to vigorous irrigation Benefit may be greater in patients with clinical fea-

tures potentially associated with a higher risk of rebleeding (eg older age concurrent illness inpatient at time bleeding began) (Conditional recommendation)

15 Endoscopic therapy should not be provided to patients who have an ulcer with a clean base or a flat pigmented spot (Strong recommendation)

16 Epinephrine therapy should not be used alone If used it should be combined with a second modality (Strong recommendation)

17 Thermal therapy with bipolar electrocoagulation or heater probe and injection of sclerosant (eg absolute alcohol) are recommended because they

reduce further bleeding need for surgery and mortality (Strong recommendation)

18 Clips are recommended because they appear to decrease further bleeding and need for surgery However comparisons of clips vs other therapies yield

variable results and currently used clips have not been well studied (Conditional recommendation)

19 For the subset of patients with actively bleeding ulcers thermal therapy or epinephrine plus a second modality may be preferred over clips or sclerosant

alone to achieve initial hemostasis (Conditional recommendation)

Medical therapy after endoscopy

20 After successful endoscopic hemostasis intravenous PPI therapy with 80 mg bolus followed by 8 mgh continuous infusion for 72 h should be given to

patients who have an ulcer with active bleeding a non-bleeding visible vessel or an adherent clot (Strong recommendation)

21 Patients with ulcers that have flat pigmented spots or clean bases can receive standard PPI therapy (eg oral PPI once daily) (Strong recommendation)

Repeat endoscopy

22 Routine second-look endoscopy in which repeat endoscopy is performed 24 h after initial endoscopic hemostatic therapy is not recommended

(Conditional recommendation)

23 Repeat endoscopy should be performed in patients with clinical evidence of recurrent bleeding and hemostatic therapy should be applied in those with

higher risk stigmata of hemorrhage (Strong recommendation)

24 If further bleeding occurs after a second endoscopic therapeutic session surgery or interventional radiology with transcathether arterial embolization is

generally employed (Conditional recommendation)








































Recommendations
































Table 1 Continued

Hospitalization



















48 Laine and Jensen









Prokinetic therapy

Recommendations























small sample (12)










Recommendations



































Gastric lavage

Recommendations





























quality evidence)





















































































0ndash4 degC (32)


Timing of endoscopy

Recommendations








50 Laine and Jensen


































Recommendations
























































Stigmata of

hemorrhage

Forrest





vessel

IIA 8

Adherent clot IIB 8


Clean base III 55





































































ENDOSCOPIC THERAPY


Recommendations





Endoscopic

therapy


Adherent clot


therapy



No endoscopic

therapy

Oral PPI



inhibitor




Stigmata

Further bleeding

(N =2994)

Surgery for

bleeding

(N =1499)

Mortality

(N =1387)


Non-bleeding

visible vessel



Flat pigmented

spot






52 Laine and Jensen












Recommendations











quality evidence)



























not seen (64)













































047ndash101) (64)













Recommendations




















other SRH

















these 1047297ndings

REPEAT ENDOSCOPY

Recommendations




























cost (64)

















the ulcer base




















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen



















































Recommendations
































Table 1 Continued

Hospitalization



















48 Laine and Jensen









Prokinetic therapy

Recommendations























small sample (12)










Recommendations



































Gastric lavage

Recommendations





























quality evidence)





















































































0ndash4 degC (32)


Timing of endoscopy

Recommendations








50 Laine and Jensen


































Recommendations
























































Stigmata of

hemorrhage

Forrest





vessel

IIA 8

Adherent clot IIB 8


Clean base III 55





































































ENDOSCOPIC THERAPY


Recommendations





Endoscopic

therapy


Adherent clot


therapy



No endoscopic

therapy

Oral PPI



inhibitor




Stigmata

Further bleeding

(N =2994)

Surgery for

bleeding

(N =1499)

Mortality

(N =1387)


Non-bleeding

visible vessel



Flat pigmented

spot






52 Laine and Jensen












Recommendations











quality evidence)



























not seen (64)













































047ndash101) (64)













Recommendations




















other SRH

















these 1047297ndings

REPEAT ENDOSCOPY

Recommendations




























cost (64)

















the ulcer base




















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen















48 Laine and Jensen









Prokinetic therapy

Recommendations























small sample (12)










Recommendations



































Gastric lavage

Recommendations





























quality evidence)





















































































0ndash4 degC (32)


Timing of endoscopy

Recommendations








50 Laine and Jensen


































Recommendations
























































Stigmata of

hemorrhage

Forrest





vessel

IIA 8

Adherent clot IIB 8


Clean base III 55





































































ENDOSCOPIC THERAPY


Recommendations





Endoscopic

therapy


Adherent clot


therapy



No endoscopic

therapy

Oral PPI



inhibitor




Stigmata

Further bleeding

(N =2994)

Surgery for

bleeding

(N =1499)

Mortality

(N =1387)


Non-bleeding

visible vessel



Flat pigmented

spot






52 Laine and Jensen












Recommendations











quality evidence)



























not seen (64)













































047ndash101) (64)













Recommendations




















other SRH

















these 1047297ndings

REPEAT ENDOSCOPY

Recommendations




























cost (64)

















the ulcer base




















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen





















quality evidence)





















































































0ndash4 degC (32)


Timing of endoscopy

Recommendations








50 Laine and Jensen


































Recommendations
























































Stigmata of

hemorrhage

Forrest





vessel

IIA 8

Adherent clot IIB 8


Clean base III 55





































































ENDOSCOPIC THERAPY


Recommendations





Endoscopic

therapy


Adherent clot


therapy



No endoscopic

therapy

Oral PPI



inhibitor




Stigmata

Further bleeding

(N =2994)

Surgery for

bleeding

(N =1499)

Mortality

(N =1387)


Non-bleeding

visible vessel



Flat pigmented

spot






52 Laine and Jensen












Recommendations











quality evidence)



























not seen (64)













































047ndash101) (64)













Recommendations




















other SRH

















these 1047297ndings

REPEAT ENDOSCOPY

Recommendations




























cost (64)

















the ulcer base




















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen















50 Laine and Jensen


































Recommendations
























































Stigmata of

hemorrhage

Forrest





vessel

IIA 8

Adherent clot IIB 8


Clean base III 55





































































ENDOSCOPIC THERAPY


Recommendations





Endoscopic

therapy


Adherent clot


therapy



No endoscopic

therapy

Oral PPI



inhibitor




Stigmata

Further bleeding

(N =2994)

Surgery for

bleeding

(N =1499)

Mortality

(N =1387)


Non-bleeding

visible vessel



Flat pigmented

spot






52 Laine and Jensen












Recommendations











quality evidence)



























not seen (64)













































047ndash101) (64)













Recommendations




















other SRH

















these 1047297ndings

REPEAT ENDOSCOPY

Recommendations




























cost (64)

















the ulcer base




















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen
















































































ENDOSCOPIC THERAPY


Recommendations





Endoscopic

therapy


Adherent clot


therapy



No endoscopic

therapy

Oral PPI



inhibitor




Stigmata

Further bleeding

(N =2994)

Surgery for

bleeding

(N =1499)

Mortality

(N =1387)


Non-bleeding

visible vessel



Flat pigmented

spot






52 Laine and Jensen












Recommendations











quality evidence)



























not seen (64)













































047ndash101) (64)













Recommendations




















other SRH

















these 1047297ndings

REPEAT ENDOSCOPY

Recommendations




























cost (64)

















the ulcer base




















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen















52 Laine and Jensen












Recommendations











quality evidence)



























not seen (64)













































047ndash101) (64)













Recommendations




















other SRH

















these 1047297ndings

REPEAT ENDOSCOPY

Recommendations




























cost (64)

















the ulcer base




















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen

















Recommendations




















other SRH

















these 1047297ndings

REPEAT ENDOSCOPY

Recommendations




























cost (64)

















the ulcer base




















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen















54 Laine and Jensen




















82 vs 87 (RR = 11 04ndash27) (91)




















population (44)















Recommendations


































are lacking



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen



































H pylori ulcers



































BLEEDING ULCERS






















H pylori

H pylori therapy


NSAID

Stop NSAID

if NSAID required

use coxib+ PPI

Low-dose aspirin

Primary CV

prevention


patients

Secondary CV

prevention


in most patients

and start PPI

Idiopathic

Maintenance PPI






56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen















56 Laine and Jensen















NSAID ulcers






























clopidogrel (128)













should be given



















































































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen


















































using NSAIDs

CONCLUSION

















undertaken










antiulcer therapy







submitted












58 Laine and Jensen














































































































60 Laine and Jensen















58 Laine and Jensen














































































































60 Laine and Jensen





































































60 Laine and Jensen














60 Laine and Jensen












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