Acute Nonvariceal Upper Gastrointestinal Bleeding

Overview and Recommendations

Background

● Acute nonvariceal upper gastrointestinal (GI) bleeding is a medical emergency involving bleeding from
a site in the GI tract that is proximal to the ligament of Treitz, most commonly within the reach of an
adult upper endoscope.

● The most common sources of acute nonvariceal bleeding are peptic ulcers, mucosal erosions
(esophagitis, gastritis, duodenitis), or Mallory-Weiss tears. Other causes include gastrointestinal
angiodysplasias (GIAD)/arteriovenous malformation, malignancy of the upper GI tract, and Dieulafoy
lesion.

● Acute nonvariceal upper GI bleeding may be associated with the use of nonsteroidal anti-
in ammatory drugs (NSAIDs) or aspirin and the presence of H. Pylori.

● Common ndings in patients who present with acute nonvariceal upper GI bleeding include:

⚬ lightheadedness, weakness, hypotension, tachycardia, or cold hands/feet due to hypovolemia or

anemia
⚬ hematemesis, co ee ground emesis, melena, or hematochezia (in the setting of rapid upper GI
bleeding)

● Hemodynamic instability at the time of presentation, presence of major comorbidities, older age, and
higher Rockall score or Albumin, International normalized ratio, Mental status, Systolic blood
pressure, age ≥ 65 (AIMS65) score are predictors of mortality. The risk of recurrence is dependent on
the nature of bleeding lesion (ulcer versus GIAD). In case of bleeding ulcers, the recurrence depends
on the ability to discontinue NSAIDS and/or eradicate H. Pylori.

Evaluation

● Assess volume status and the need for aggressive resuscitation (Strong recommendation).

● Assess coagulation status and the need to correct anticoagulation.

● Use an initial (pre-endoscopic) risk scale such as Rockall, Glasgow-Blatchford, or AIMS65 score to
stratify patient risk (Strong recommendation). Consider hospital discharge for outpatient endoscopy
for patients with a Glasgow-Blatchford score of 0 or 1 (Strong recommendation), which includes the
following:
⚬ urea nitrogen < 18.2 mg/dL
⚬ hemoglobin ≥ 13 g/dL for men (12 g/dL for women)
⚬ systolic blood pressure ≥ 110 mm Hg
⚬ pulse < 100 beats/minute
⚬ absence of melena, syncope, cardiac failure, and liver disease

● Nasogastric or orogastric lavage is not routinely recommended, especially in those who are actively
anticoagulated; consider in select patients (Weak recommendation). Blood or co ee-ground-like
material suggests the likelihood of upper GI bleeding and may suggest a high-risk lesion, but negative
aspirate may not rule out upper GI bleeding.
● Perform esophagogastroduodenoscopy (EGD) as soon as the patient is hemodynamically stabilized
(within 24 hours if possible) (Strong recommendation).

Management

● Start uid resuscitation with crystalloid solutions (Strong recommendation) and transfuse red blood
cells for hemoglobin < 7 g/dL (Strong recommendation). Correct coagulopathy if present in patients
without absolute contraindications, but correction should not delay endoscopy (Strong
recommendation).

● Fluids should be titrated carefully, even in the context of uid responsiveness, and especially in the
presence of elevated intravascular lling pressures or extravascular lung water.

● Consider a higher hemoglobin target of 8 g/dL in the following two clinical scenarios and until their
resolution: presence of hypotension and active cardiac ischemia (Strong recommendation).

● Consider endotracheal intubation prior to endoscopy to protect from potential aspiration in patients
with ongoing active hematemesis, encephalopathy, or agitation (Weak recommendation).

● For treatment of acute varices, see Acute variceal hemorrhage.

● For peptic ulcer bleeding:

⚬ Start IV continuous proton pump inhibitor infusion therapy before endoscopy to decrease
likelihood of higher risk stigmata of hemorrhage at endoscopy, but do not delay endoscopy (Strong
recommendation).
⚬ Treat high-risk stigmata (active bleeding, visible vessel, adherent clot) with endoscopic therapy to
reduce further bleeding and surgery (Strong recommendation). Options include epinephrine
injection (should not be used alone), thermocoagulation, mechanical hemostasis (clips), and
injection of sclerosant therapy; glue or adhesive injection reserved for second-line treatment.

● For GI angiodysplasias or Mallory-Weiss or Dieulafoy lesions, provide endoscopic hemostasis in the

setting of active bleeding (Strong recommendation).

● After successful endoscopic hemostasis of ulcer, start proton pump inhibitor therapy (such as
omeprazole or pantoprazole 80 mg IV bolus then 8 mg/hour infusion for 72 hours) for peptic ulcers
(Strong recommendation). EradicateHelicobacter pylori if present (Strong recommendation). Negative
H. pylori tests during active hemorrhage should be repeated after hemorrhage resolution due to the
high false-negative results rate (Strong recommendation).

● For patients with nonsteroidal anti-in ammatory drug (NSAID) induced ulcer bleeding, resume NSAIDs
after achievement of hemostasis unless the NSAIDS can be safely discontinued (Strong
recommendation).

● For patients with previous NSAID induced ulcer bleeding who require NSAIDs, switch to a combination
of proton-pump inhibitor (PPI) and cyclooxygenase-2 (COX-2) inhibitor at lowest e ective dose to
reduce risk of rebleeding (Strong recommendation). If COX-2 inhibitors (such as Celecoxib) are
contraindicated by allergies or comorbidities then use a PPI with alternative NSAID.

● For esophagitis, treat with proton pump inhibitor therapy. Patients with severe esophagitis (Los
Angeles esophagitis classi cation Grade C or D, or stricture) may require increased, twice-daily
standard PPI dosing.
● For rebleeding, repeat the upper endoscopy and attempt hemostasis. For uncontrolled bleeding or for
rebleeding that cannot be controlled with a repeat endoscopy, consider 1 of the following depending
on the clinical presentation of the patient and of the bleeding:
⚬ angiography selective arterial embolization (Weak recommendation)
⚬ surgery (Weak recommendation)

● When EGD does not reveal a source of bleeding and there is a high suspicion of an upper GI bleed,
consider evaluation for suspected small bowel bleeding.

Related Summaries

● Acute lower gastrointestinal bleeding in adults

● Acute gastritis

● Acute variceal hemorrhage

● Gastrointestinal angiodysplasia

● Peptic ulcer disease

Hospitalist Focused Content

Content referenced with “Consensus” in Hospitalist Focused Content is supported by a combination of
the best available evidence and expert opinion put forth by a panel of Hospitalists.

Panel participants:

● Vijay Duggirala, MD: Clinical Assistant Professor, The Ohio State University College of Nursing; Clinical
Assistant Professor, The Ohio State University College of Medicine; Hospitalist, Director of Consult
Services and Director of Quality & Patient Safety, Division of Hospital Medicine, The Ohio State Wexner
Medical Center; Ohio, United States

● Dr. Duggirala declares no relevant nancial con icts of interest.

● Chi Huang, MD: Executive Medical Director of General Medicine and Hospital Medicine Shared
Services, Wake Forest Baptist Health System; Section Chief, Hospital Medicine, Wake Forest Baptist
Medical Center; Associate Professor of Internal Medicine, Wake Forest Medical School; North Carolina,
United States

● Dr. Huang declares no relevant nancial con icts of interest.

● Richard Rothman, MD: Chair and Physician Advisor, Department of Hospital Medicine, Cleveland Clinic
India River Hospital; Florida, United States

● Dr. Rothman declares no relevant nancial con icts of interest.

● Andrés J. Solorza, MD: Assistant Clinical Professor, Tufts University; Chair-Person, Department of
Hospital Medicine, Lahey Hospital and Medical Center; Massachusetts, United States

● Dr. Solorza declares no relevant nancial con icts of interest.

● Nestor G. Tarragona, MD, FHM, FACP: Assistant Professor of Medicine, Tufts University School of
Medicine; Vice Chairperson, Division of Hospital Medicine, Lahey Hospital and Medical Center; Medical
Director for Latin America, Teladoc Health; Massachusetts, United States

● Dr. Tarragona declares no relevant nancial con icts of interest.

● Yoania Quintana-Garcia, MD: Hospitalist, Cleveland Clinic Indian River Hospital; Florida, United States

● Dr. Quintana-Garcia declares no relevant nancial con icts of interest.

Admission Checklists

General Admission Checklist

● Determine code statusConsensus

● Establish IV accessConsensus

● Determine appropriate treatment settingConsensus

● Diet should be nothing per mouth (NPO) on admissionConsensus

● Communicate with outpatient primary care provider (PCP) to obtain:Consensus

⚬ Outpatient advanced directives

⚬ Problem list
⚬ Reconciled medication list
⚬ Medical and surgical history
⚬ List of other healthcare providers involved

● Engage in collaborative care management with the PCP during hospital stayConsensus

Admission Checklist for Patients With Acute Nonvariceal Upper Gastrointestinal Bleeding

● Assess volume status using physiologic parameters and trend hemoglobin serially (will lag behind
clinical change)Consensus

● Supine hypotension (hypovolemic shock) is an end-stage nding corresponding to > 30%-40% loss of
circulating blood loss that indicates the need for emergent stabilization and intervention (J Trauma
2008 Jun;64(6):1638 )

● Ensure adequate IV access to allow for rapid resuscitation (typically 100-200 mL/minute, equivalent to
2, 18-gauge peripheral IVs)Consensus

● Ensure type and hold is drawn and blood availableConsensus

● Consider mechanical deep vein thrombosis prophylaxis in patients with active gastrointestinal (GI)
bleedingConsensus

● Check renal function, complete blood count, and coagulation (partial thromboplastin time [PTT] and
international normalized ratio [INR])Consensus
● Start uid resuscitation with crystalloid solutions (ACG Strong recommendation; ESGE Strong
recommendation, Moderate-quality evidence) and transfuse red blood cells for hemoglobin < 7 g/dL
in hemodynamically stable patients with acute gastrointestinal bleeding (ACG Conditional
recommendation; ESGE Strong recommendation, Moderate-quality evidence) 4 , 6 ; in patients with
renal insu ciency or acute renal failure balanced crystalloids such as Lactated Ringers may be
preferable (N Engl J Med 2018 Mar 1;378(9):829 full-text , N Engl J Med 2018 Mar 1;378(9):819
full-text )

● Consider a higher hemoglobin target if there is clinical evidence of hypotensive shock or

comorbidities, such as coronary artery disease (ICUGB Conditional recommendation, Very low-quality
evidence; ACG Conditional recommendation; ESGE Strong recommendation, Moderate-quality
evidence), or if high suspicion of vigorous active ongoing bleeding or an uncorrected coagulopathy
exists 2 , 4 , 6

● Correct coagulopathy if present in patients without absolute contraindications (ESGE Strong

recommendation, Low-quality evidence) 6

● Fluids should be titrated carefully, even in the context of uid responsiveness, and especially in the
presence of elevated intravascular lling pressures or extravascular lung water (Intensive Care Med
2014 Dec;40(12):1795 full-text )

● Consider endotracheal intubation prior to endoscopy to protect from potential aspiration in patients
with ongoing active hematemesis, encephalopathy, or agitation (ESGE Weak recommendation, Low-
quality evidence) 6

● For suspected peptic ulcer or unknown-cause presumed upper GI bleeding: start proton pump
inhibitor (PPI) therapy (preferable by IV bolus) before endoscopy to decrease likelihood of higher risk
stigmata (active bleeding or visible vessel) (ACG Conditional recommendation; ESGE Strong
recommendation, High-quality evidence), but do not delay endoscopy (ICUGB Grade 1B; ESGE Strong
recommendation, High-quality evidence) 2 , 6

● For patients with bleeding ulcers with high-risk stigmata who have undergone successful endoscopic
therapy, we recommend using PPI therapy via IV loading dose followed by continuous IV infusion (as
opposed to no treatment or H2-receptor antagonists) (ICUGB Strong recommendation, Moderate-
quality evidence; ACG Strong recommendation; ESGE Strong recommendation, High-quality
evidence) 2 , 4 , 6

● Ulcers and other causes of GI bleeding may lead to mild discomfort but will not cause peritonitis;
acute abdominal ndings warrant imaging and emergent surgical consultation to assess for
perforationConsensus

● Individualize the decision to stop any nonsteroidal anti-in ammatory drugs (NSAIDs) or other
antiplatelet therapy based on the risk of thrombosis if stopped and the severity of bleeding
(Gastrointest Endosc 2016 Jan;83(1):3 , correction in Gastrointest Endosc 2016 Mar;83(3):678);
aspirin for primary prevention should generally be stoppedConsensus

● Discuss erythromycin (250 mg IV) with consulting gastroenterologist to enhance endoscopic

visualization (does not a ect clinical outcomes) (Ann Gastroenterol 2016 Jul;29(3):312 full-text )
● Nasogastric/orogastric (NG/OG) lavage has a poor sensitivity and should not be routinely employed

(ESGE Strong recommendation, Moderate-quality evidence) 6

● Evaluate for signs/symptoms of special cases that may indicate a more likely cause of bleeding and
require pre-endoscopy therapy including (see Causes in Acute nonvariceal upper gastrointestinal
bleeding):
⚬ Variceal: treat as a potential variceal bleed if there is known or suspected cirrhosis 5

⚬ Aorto-enteric stula: should be considered in any patient with a prior surgical aneurysm repair;
consider cross-sectional vascular imaging (for example, computerized tomogram angiography
[CTA])

● Upper endoscopy should generally be done within 24 hours of admission for all upper GI bleeding
(ICUGB Conditional recommendation, Very low-quality evidence; ACG Conditional recommendation)
and should be done after initial resuscitation (ACG Conditional recommendation) 2 , 4

● Most predictive ndings to diagnose acute upper GI bleeding appear to be melena on exam, history of
upper GI bleed, and positive nasogastric lavage, while syncope, cirrhosis, malignancy, hemoglobin < 8
g/dL, and pulse > 100 may predict severe bleed DynaMed Level 2 (JAMA 2012 Mar 14;307(10):1072
)

Treatment Setting

All patients with clinically suspected upper gastrointestinal (GI) bleeding should be referred to the
hospital for triage and evaluation.Consensus

Most patients with acute upper GI bleeding will require hospitalization.Consensus

Patients with a Glasgow Blatchford score of 0 (ACG Conditional recommendation; ESGE Strong
recommendation, Moderate-quality evidence) or 1 (ESGE Strong recommendation, Moderate-quality
evidence) may be considered for discharge from emergency department without inpatient endoscopy
(advise patients of risk of recurrent bleeding). 4 , 6

Patients with hematochezia (not melena) presumed due to upper GI bleed or any signs of hemodynamic
instability (resting tachycardia, orthostatic hypotension) should be considered for admission to the
intensive care unit (ICU).Consensus

Patients with ongoing hematemesis should generally be triaged to the ICU.Consensus

Consultation and Referral

Ensure early gastroenterology consultation for assistance in diagnostic/therapeutic interventions;

typically upper endoscopy is appropriate in nearly all cases of con rmed or suspected upper
gastrointestinal (GI) bleed most often within 24 hours. 6

Interventional radiology (for embolization) or surgical consultation should be considered for patients not
amenable to endoscopic therapy or with a known etiology not amenable to endoscopic
intervention.Consensus

Consider consultation with a hematologist for ongoing coagulopathy. 6

Cardiology and/or neurology consultation may be appropriate to assist in determining risk of holding
anticoagulant and or antithrombotic therapy. 6 , Consensus
Consultation with an intensivist is recommended for patients who are hemodynamically
unstable.Consensus

General Discharge Planning

Start discharge planning on hospital day one. (J Hosp Med 2013 Aug;8(8):421 )

All patients need to have documented clinical stability including stable blood counts and cessation of
clinical evidence of bleeding prior to discharge (ACG Strong recommendation). 4

Instruct patients on what is meant by nonsteroidal anti-in ammatory drugs (NSAIDs) and avoidance if
applicable to reduce the risk of recurrent bleeding.Consensus

Provide instruction on when to restart platelet inhibitor in the setting of upper GI bleed.Consensus

Instruct patients on proper dosing and timing of proton-pump inhibitors (PPIs).Consensus

Ensure patients understand the signs and symptoms of recurrent GI bleeding and are instructed on
return precautions:
● If appropriate, educate the patient on treatment and posttreatment testing for Helicobacter
pyloriConsensus

● If the source of bleeding requires ongoing management, ensure appropriate follow-up or

multidisciplinary specialty care is in place, for example:Consensus
⚬ New gastric cancer should have surgical oncology and medical oncology follow-up
⚬ Bleeding from arterio-venous malformations is generally chronic and patients should have
gastroenterology and hematology follow-up

● Educate patient on smoking cessation if applicable to assist in healing 3

Discharge Planning for Patients With Acute Nonvariceal Upper Gastrointestinal

Bleeding

Diet may be restarted immediately after endoscopy in stable patients with a clean-based ulcer with no
clinical signs of ongoing bleeding (ACG Strong recommendation). 4

Discharge can be considered immediately postendoscopy in stable patients with a clean-based ulcer
provided they have good follow-up and a good understanding of when to return (ACG Strong
recommendation). 4

Patients requiring treatment of their ulcer due to higher-risk stigmata of bleeding or active bleeding
should be observed as an inpatient for at least 3 days and initially start with clear liquids postendoscopy
prior to advancing diet (ACG Conditional recommendation). 4

Discharge Checklist

● Ensure cessation of clinical evidence of bleedingConsensus

● Arrange prompt outpatient care follow-up to include blood counts within 1 week or sooner for
bleeding requiring intensive care unit (ICU) stayConsensus

● Discuss the risk of re-bleeding with the patient based on underlying etiologyConsensus
● Verify the need (if any) for specialist follow-up as an outpatient in addition to primary careConsensus

● Aspirin for secondary prevention of cardiovascular events should be restarted within 1 week and
ideally within 72 hours in conjunction with daily proton-pump inhibitor (PPI) therapy (Gastrointest
Endosc 2016 Jan;83(1):3 , correction in Gastrointest Endosc 2016 Mar;83(3):678); aspirin for primary
prevention of cardiovascular events should generally be discontinuedConsensus

● Discontinue nonsteroidal anti-in ammatory drugs (NSAIDs) if possible; if NSAIDs must be resumed,
consider COX-2 selective NSAID at the lowest e ective dose plus daily PPI (ICUGB Grade 1B; ACG
Strong recommendation) ( 2 , 4 , Ann Intern Med 2010 Jan 19;152(2):101 full-text ):
⚬ Any patients on long-term NSAIDs or with Helicobacter pylori-negative ulcer should be prescribed
inde nite PPI therapy
⚬ Negative H. pylori tests during active bleeding should be repeated after hemorrhage resolution due

to high false-negative result rate 2 , 6

⚬ Restart anticoagulation and antiplatelet agents if there is an ongoing indication as long as the

source of bleeding is controlled 6

⚬ Patients with bleeding ulcers should be tested for H. pylori infection (ACG Strong recommendation;

ESGE Strong recommendation, Low-quality evidence) 4 , 6 and treatment with interval repeat
testing arranged for outpatient (no need to treat inpatient)
⚬ Ensure repeat endoscopy in 8-12 weeks for any patients with a gastric ulcer 3

● Assure follow-up appointment in about 2-7 days with primary care providerConsensus

General Information

Description

● common medical emergency involving gastrointestinal tract bleeding above ligament of Treitz, which

may include sites in esophagus, stomach, and/or duodenum 1 , 3

Definitions

● gastrointestinal bleeding can be classi ed into 3 clinical presentations

⚬ overt - clinically visible bleeding (hematemesis, hematochezia, or melena)

⚬ occult - bleeding that is not clinically visible, but detected by positive fecal occult blood test or iron
de ciency anemia
⚬ obscure - recurrent bleeding in which site remains undetermined after evaluation of upper
gastrointestinal tract, small bowel, and colon using multiple diagnostic modalities (may be
classi ed as overt or occult depending on clinical presentation)
⚬ Reference - Med Clin North Am 2016 Sep;100(5):1047

Epidemiology

Incidence/Prevalence

● estimated annual incidence 50-150 episodes per 100,000 adults 5

● accounts for > 300,000 hospital admissions annually (Gastrointest Endosc Clin N Am 2015 Jul;25(3):415
)

STUDY
● SUMMARY
incidence of upper gastrointestinal bleeding or perforation in general population about 1 per
1,000 person-years

SYSTEMATIC REVIEW: J Clin Epidemiol 2002 Feb;55(2):157

Details
⚬ based on systematic review of 12 population-based studies reporting incidence of serious upper
gastrointestinal complications in adults who were not regularly using nonsteroidal anti-
in ammatory drugs (NSAIDs)
⚬ studies limited to those published between 1980 and 2000
⚬ pooled incidence estimates among nonusers of prescription NSAIDs per 1,000 person-years

– 0.9 (95% CI 0.66-1.27) for bleeding or perforated lesions

– 0.1 (95% CI 0.04-0.23) for perforations alone
– 0.8 (95% CI 0.58-0.68) for bleeding lesions alone
– 1 (95% CI 0.83-1.15) for serious gastrointestinal ulcer (complicated or without bleeding)

⚬ rates increased with age and male gender

⚬ Reference - J Clin Epidemiol 2002 Feb;55(2):157

STUDY
● SUMMARY
incidence of gastrointestinal bleeding 1.2 per 1,000 patient-days in critically ill patients
receiving stress ulcer prophylaxis during intensive care unit stay

COHORT STUDY: Chest 2018 Sep;154(3):557

Details
⚬ based on retrospective cohort study
⚬ 70,093 critically ill adults receiving proton pump inhibitors or histamine-2 receptor agonists for ≥ 3
days for stress ulcer prophylaxis during intensive care unit stay between 2008 and 2012 were
assessed
⚬ 71% received proton pump inhibitor and 30% received histamine-2 receptor agonist
⚬ > 50% of patients received anticoagulants, antiplatelet agents, or nonsteroidal anti-in ammatory
drugs during intensive care unit stay (median length of stay 7 days)
⚬ 0.6% had incident clinically signi cant gastrointestinal bleeding (incidence rate 1.2 cases per 1,000
patient-days)
⚬ Reference - Chest 2018 Sep;154(3):557

Risk factors

Antiplatelet drugs (including nonsteroidal anti-inflammatory drugs [NSAIDs])

● aspirin

STUDY
⚬ SUMMARY
long-term aspirin associated with increased risk for gastrointestinal bleeding at any dose

SYSTEMATIC REVIEW: BMJ 2000 Nov 11;321(7270):1183

 Details
– based on systematic review
– systematic review of 24 randomized trials comparing aspirin therapy vs. placebo for ≥ 1 year
(mean 28 months) in 65,987 patients
– review included trials reporting all gastrointestinal bleeding (including melena and
hematochezia), and excluded trials reporting only subcategories of bleeding (such as bleeding
requiring hospitalization or blood transfusion)
– gastrointestinal bleeding comparing aspirin vs. no aspirin

● in 2.47% vs. 1.43% overall (odds ratio [OR] 1.68, 95% CI 1.51-1.88, NNH 96)
● in 2.3% vs. 1.45% with aspirin dose < 163 mg/day (OR 1.59, 95% CI 1.4-1.81, NNH 117)
● in 2.98% vs.1.35% with aspirin doses 163-1,500 mg/day (OR 1.96, 95% CI 1,58-2.4, NNH 61)

– no relation between risk for bleeding and dose or modi ed formulation

– Reference - BMJ 2000 Nov 11;321(7270):1183
– previous meta-analysis which evaluated risk for major gastrointestinal bleeding did nd dose-
response relationship (editorial in BMJ 2000 Nov 11;321(7270):1170 )

⚬ low-dose aspirin associated with 2 times risk for upper gastrointestinal complications (bleeding or
perforation) in case-control studies, similar risk with enteric-coated preparation (BMC Clin
Pharmacol 2001;1:1 )

● NSAIDs

STUDY
⚬ SUMMARY
risk factors for upper gastrointestinal bleeding may include older age, history of peptic ulcer
disease, male sex, and nonsteroidal anti-inflammatory drug (NSAID) use

SYSTEMATIC REVIEW: Arch Intern Med 2000 Jul 24;160(14):2093 | Full Text

Details
– based on systematic review of 15 case-control and 3 cohort studies published in 1990s
– increased risk with NSAIDs was dose-dependent
– risk di erences between individual NSAIDs reduced when considering comparable daily doses
– Reference - Arch Intern Med 2000 Jul 24;160(14):2093 full-text

STUDY
⚬ SUMMARY
risk of upper gastrointestinal bleeding and perforation differs among NSAIDs

SYSTEMATIC REVIEW: Arthritis Rheum 2010 Jun;62(6):1592 | Full Text

CASE-CONTROL STUDY: Pharmacotherapy 2009 Dec;29(12):1397

Details
– based on 1 systematic review and 1 nested case-control study
– systematic review of 2 cohort studies and 7 case-control studies with data on NSAID use and
upper gastrointestinal bleeding in 51,594 patients
● pooled risk of upper gastrointestinal bleeding/perforation

⚬ for all traditional NSAIDS (relative risk [RR] 4.5, 95% CI 3.82-5.31)
⚬ for COX-2 selective inhibitors (RR 1.88, 95% CI 0.96-3.71), results may be limited by
heterogeneity (p = 0.019)
 ● pooled risk of upper gastrointestinal bleeding/perforation with individual NSAIDs

⚬ lower risk than for all traditional NSAIDs

– celecoxib (RR 1.42, 95% CI 0.85-2.4) in analysis of 4 studies

– rofecoxib (RR 2.12, 95% CI 1.6-2.8) in analysis of 5 studies
– ibuprofen (RR 2.69, 95% CI 2.2-3.3) in analysis of 5 studies
– aceclofenac (RR 1.44, 95% CI 0.65-3.2) in analysis of 3 studies

⚬ medium risk

– diclofenac (RR 3.98, 95% CI 3.4-4.7) in analysis of 6 studies

– meloxicam (RR 4.15, 95% CI 2.6-6.6) in analysis of 4 studies
– indomethacin (RR 5.4, 95% CI 4.2-7) in analysis of 5 studies
– naproxen (RR 5.63, 95% CI 3.8-8.3) in analysis of 6 studies
– ketoprofen (RR 5.57, 95% CI 3.9-7.9) in analysis of 5 studies

⚬ higher risk than for all traditional NSAIDS

– piroxicam (RR 9.94, 95% CI 6-16.5) in analysis of 5 studies

– ketorolac (RR 14.54, 95% CI 5.9-36) in analysis of 2 studies

● pooled risk associated with dosage or duration of traditional NSAID use

⚬ for low dose (RR 2.79, 95% CI 2.2-3.6) in analysis of 3 studies

⚬ for high dose (RR 5.36, 95% CI 4.6-6.3) in analysis of 4 studies
⚬ for duration of use 1-30 days (RR 5.22, 95% CI 3.8-7.2) in analysis of 3 studies
⚬ for duration of use > 365 days (RR 2.9, 95% CI 2.2-3.8) in analysis of 3 studies

● Reference - Arthritis Rheum 2010 Jun;62(6):1592 full-text , editorial can be found in

Arthritis Rheum 2010 Jun;62(6):1568
– nested case-control study of 726 patients aged 20-89 years with upper gastrointestinal
complications and 20,002 control patients
● lower risk - celecoxib (odds ratio [OR] 1.1, 95% CI 0.7-1.8), diclofenac plus misoprostol (OR
0.7, 95% CI 0.3-1.8)
● higher risk - rofecoxib (OR 3.6, 95% CI 2.2-5.7), naproxen (OR 3.4, 95% CI 1.8-6.7)
● Reference - Pharmacotherapy 2009 Dec;29(12):1397

–
DynaMed Commentary

Rofecoxib (Vioxx) was withdrawn from the market in 2004 for cardiovascular toxicity.

STUDY
● SUMMARY
use of most antiplatelet agents appears to increase risk of peptic ulcer-related upper
gastrointestinal bleeding

CASE-CONTROL STUDY: Gut 2006 Dec;55(12):1731 | Full Text

Details
⚬ based on case-control study
⚬ 2,777 patients (mean age 61 years) with endoscopy-proven major upper gastrointestinal bleeding
(UGIB) due to peptic ulcer lesion were compared to 5,532 age-matched controls
⚬ 24% of cases and 9% of controls had taken ≥ 1 non-aspirin NSAID in week before hospital
admission
 ⚬ increased risk of UGIB associated with current use of

– current nonaspirin NSAIDs use (adjusted relative risk [RR] 5.3, 95% CI 4.5-6.2) with risk lowest for
aceclofenac (adjusted RR 2.6) and highest for ketorolac (adjusted RR 14.4)
– rofecoxib (adjusted RR 2.1, 95% CI 1.1-4)
– aspirin (adjusted RR 5.3, 95% CI 4.5-6.3)
– cardioprotective aspirin (100 mg/day) (adjusted RR 2.7, 95% CI 2-3.6)
– nonaspirin antiplatelet treatment (clopidogrel or ticlopidine) (adjusted RR 2.8, 95% CI 1.9-4.2)
– anticoagulants (adjusted RR 2.8, 95% CI 2.1-3.7)

⚬ no signi cant increase in risk of UGIB with

– celecoxib
– acetaminophen
– NSAID plus proton pump inhibitor

⚬ Reference - Gut 2006 Dec;55(12):1731 full-text

Combination of anticoagulant and antiplatelet drugs

STUDY
● SUMMARY
addition of anticoagulants or clopidogrel to daily low-dose aspirin may increase risk of major
gastrointestinal bleeding

RANDOMIZED TRIAL: Clin Gastroenterol Hepatol 2011 Sep;9(9):762

Details
⚬ based on systematic review of 61 randomized trials evaluating low-dose aspirin (75-325 mg/day)
alone or with other medication with data on adverse events
⚬ increased risk of major gastrointestinal bleeding associated with

– aspirin plus anticoagulants compared to aspirin alone (odds ratio [OR] 1.93, 95% CI 1.42-2.61)
– aspirin plus clopidogrel compared to aspirin alone (OR 1.86, 95% CI 1.49-2.31)
– aspirin alone compared to placebo (OR 1.55, 95% CI 1.27-1.9)

⚬ Reference - Clin Gastroenterol Hepatol 2011 Sep;9(9):762

STUDY
● SUMMARY
combination of anticoagulants and antiplatelet drugs may be associated with greater risk of
gastrointestinal bleeding than monotherapy

CASE-CONTROL STUDY: CMAJ 2007 Aug 14;177(4):347 | Full Text

Details
⚬ based on case-control study with 4,028 adults > 18 years old with rst-ever diagnosis of
gastrointestinal bleeding and 40,171 matched controls assessed for antithrombotic drug exposure
(de ned as prescription issued within 90 days before index event)
⚬ adjusted rate ratio by drug exposure

– 1.94 (95% CI 1.61-2.34) for warfarin

– 1.39 to 1.78 for antiplatelet drugs, including

● 1.78 (95% CI 1.61-1.97) for NSAIDs

● 1.67 (95% CI 1.27-2.2) for clopidogrel
● 1.64 (95% CI 1.31-2.06) for COX-2 inhibitor
● 1.39 (95% CI 1.26-1.53) for aspirin
 – 2.6 to 3.9 for combinations of antiplatelet agents, including

● 3.9 (95% CI 2.78-5.47) for clopidogrel plus aspirin

● 2.9 (95% CI 1.58-5.35) for clopidogrel plus NSAID
● 2.6 (95% CI 1.09-6.23) for clopidogrel plus COX-2 inhibitor

– 4.62 to 6.48 for warfarin plus antiplatelet agents

● 6.48 (95% CI 4.25-9.87) for warfarin plus aspirin

● 4.79 (95% CI 2.79-8.21) for warfarin plus NSAID
● 4.62 (95% CI 1.48-14.43) for warfarin plus COX-2 inhibitor

⚬ Reference - CMAJ 2007 Aug 14;177(4):347 full-text , commentary can be found in CMAJ 2008
Jan 29;178(3):327

STUDY
● SUMMARY
antiplatelet agents and vitamin K antagonists appear to increase risk of serious upper
gastrointestinal bleeding individually and additively

CASE-CONTROL STUDY: BMJ 2006 Oct 7;333(7571):726 | Full Text

Details
⚬ based on case-control study comparing 1,443 cases of serious upper gastrointestinal bleeding not
due to gastric varices with 57,720 matched controls in Denmark
⚬ adjusted odds ratios for upper gastrointestinal bleeding

– 7.4 (95% CI 3.5-15) for clopidogrel plus aspirin

– 5.3 (95% CI 2.9-9.5) for vitamin K antagonists plus aspirin
– 2.3 (95% CI 1.7-3.3) for dipyridamole plus aspirin
– 1.9 (95% CI 1.3-2.8) for dipyridamole
– 1.8 (95% CI 1.5-2.1) for low-dose aspirin
– 1.8 (95% CI 1.3-2.4) for vitamin K antagonists
– 1.1 (95% CI 0.6-2.1) for clopidogrel

⚬ Reference - BMJ 2006 Oct 7;333(7571):726 full-text , editorial can be found in BMJ 2006 Oct
7;333(7571):712 , commentary can be found in Am Fam Physician 2007 Apr 1;75(7):1068

Novel oral anticoagulants (NOACs)

STUDY
● SUMMARY
novel oral anticoagulants and conventional anticoagulants associated with similar risk of major
gastrointestinal bleeding, but dabigatran and rivaroxaban might increase risk of bleeding
compared to conventional anticoagulants

SYSTEMATIC REVIEW: Clin Gastroenterol Hepatol 2017 Nov;15(11):1674-1683.e3

Details
⚬ based on systematic review with trial-speci c quality measures not reported
⚬ systematic review of 43 randomized trials comparing novel oral anticoagulants (NOACs) vs.
conventional anticoagulants or placebo in 166,289 patients
– NOACs were dabigatran (11 trials), rivaroxaban (14 trials), apixaban (10 trials), edoxaban (7
trials), or betrixaban (1 trial)
– NOACs compared to warfarin (18 trials), enoxaparin (18 trials), placebo (6 trials), or aspirin (1
trial)
 – trials compared NOACs vs. conventional anticoagulants or placebo for atrial brillation (8 trials),
venous thromboembolism (VTE) treatment (13 trials), or VTE prophylaxis (22 trials)
⚬ comparing NOACs vs. conventional anticoagulants or placebo, no signi cant di erence in risk of

– major GI bleeding in analysis of 28 trials with 129,357 patients, results limited by signi cant
heterogeneity
– clinically relevant nonmajor GI bleeding in analysis of 8 trials with 16,969 patients
– upper GI bleeding in analysis of 4 trials with 23,224 patients
– lower GI bleeding in analysis of 4 trials with 23,211 patients

⚬ in subgroup analysis comparing individual NOACs vs. conventional anticoagulants or placebo

– dabigatran associated with increased major GI bleeding in analysis of 5 trials with 27,485
patients
● odds ratio 1.27 (95% CI 1.04-1.55)
● NNH 142-1,949 with 1.3% major GI bleeding in conventional anticoagulants or placebo group
● no signi cant di erence in sensitivity analysis excluding largest trial with longest duration
and highest GI bleeding rate in NOAC group
– rivaroxaban associated with increased major GI bleeding in analysis of 8 trials with 27,175
patients
● odds ratio 1.4 (95% CI 1.15-1.7)
● NNH 112-520 with 1.3% major GI bleeding in conventional anticoagulants or placebo group
● no signi cant di erence in sensitivity analysis excluding largest trial with longest duration
and highest GI bleeding rate in NOAC group
– no signi cant di erence in bleeding

● comparing apixaban and conventional anticoagulants or placebo in analysis of 9 trials with

43,647 patients
● comparing edoxaban and conventional anticoagulants or placebo in analysis of 6 trials with
31,050 patients
⚬ Reference - Clin Gastroenterol Hepatol 2017 Nov;15(11):1674-1683.e3

Risk factors in critically ill patients

STUDY
● SUMMARY
mechanical ventilation for > 48 hours and coagulopathy each associated with increased risk of
gastrointestinal bleeding in critically ill adults

COHORT STUDY: N Engl J Med 1994 Feb 10;330(6):377 | Full Text

Details
⚬ based on prospective cohort study
⚬ 2,252 adults > 16 years old admitted to intensive care units were evaluated for risk factors for
stress-related mucosal bleeding
⚬ 30% received stress ulcer prophylaxis due to

– constipation or prior diagnosis of peptic ulcer disease and gastritis

– receiving drugs that increase risk of bleeding
– overt bleeding
– unspeci ed indications

⚬ clinically important bleeding, de ned as overt bleeding in association with hemodynamic

compromise or need for blood transfusion, in
 – 1.5% of all patients
– 3.7% of 847 high-risk patients (with 1 or 2 risk factors)
– 0.1% of 1,405 low-risk patients (with 0 risk factors)

⚬ factors associated with clinically important bleeding in multivariate analysis

– respiratory failure requiring mechanical ventilation > 48 hours (odds ratio [OR] 15.6, p < 0.001)
– coagulopathy (OR 4.3, p < 0.001)
– hypotension (OR 3.7, p = 0.08)

⚬ Reference - N Engl J Med 1994 Feb 10;330(6):377 full-text , editorial can be found in N Engl J
Med 1994 Feb 10;330(6):428 , commentary can be found in N Engl J Med 1994 Jul 7;331(1):52

Medications

● selective serotonin reuptake inhibitor (SSRI) antidepressants

STUDY
⚬ SUMMARY
selective serotonin reuptake inhibitors (SSRIs) associated with increased risk of upper
gastrointestinal bleeding

SYSTEMATIC REVIEW: Am J Gastroenterol 2014 Jun;109(6):811

Details
– based on systematic review of observational studies
– systematic review of 19 observational studies (4 cohort and 15 case-control studies) evaluating
association between SSRIs and risk of upper gastrointestinal bleeding in more than 390,000
adults
– control included placebo or no treatment
– all results were limited by signi cant heterogeneity
– SSRI use (without nonsteroidal anti-in ammatory drugs [NSAIDs]) associated with increased risk
of upper gastrointestinal bleeding
● in analysis of 15 case-control studies (odds ratio [OR] 1.66, 95% CI 1.44-1.92)
● in analysis of 4 cohort studies (OR 1.68, 95% CI 1.13-2.5)

– use of both SSRIs and NSAIDs associated with increased risk of upper gastrointestinal bleeding

● in analysis of 10 case-control studies (OR 4.25, 95% CI 2.82-6.42)

● in analysis of 2 cohort studies (OR 6.08, 95% CI 1.59-23.39)

– Reference - Am J Gastroenterol 2014 Jun;109(6):811

STUDY
⚬ SUMMARY
antidepressants that inhibit serotonin reuptake associated with increased risk for upper
gastrointestinal bleeding

COHORT STUDY: BMJ 2001 Sep 22;323(7314):655 | Full Text

Details
– based on retrospective population-based cohort study
– 317,824 older patients taking antidepressants observed for > 130,000 person-years
– 974 were admitted to hospital for acute upper gastrointestinal bleeding (7.3 per 1,000 person-
years)
– antidepressants classi ed according to degree of inhibition of serotonin reuptake
risk of bleeding increased with increasing inhibition of serotonin reuptake
 – potentially clinically signi cant in 2 subgroups
–

● patients > 80 years old (10.6 bleeds per 1,000 person-years with low inhibition of serotonin
reuptake vs. 14.7 with high inhibition of serotonin reuptake, NNH 244)
● patients with previous upper gastrointestinal bleeding (28.6 bleeds per 1,000 person-years
with low inhibition of serotonin reuptake vs. 40.3 with high inhibition of serotonin reuptake,
NNH 85)
– Reference - BMJ 2001 Sep 22;323(7314):655 full-text , summary can be found in Am Fam
Physician 2002 Apr 1;66(7):1435

● steroids

STUDY
⚬ SUMMARY
corticosteroids might be associated with increased risk of gastrointestinal bleeding or
perforation in hospitalized patients

SYSTEMATIC REVIEW: BMJ Open 2014 May 15;4(5):e004587 | Full Text

Details
– based on systematic review
– systematic review of 159 randomized trials comparing corticosteroids to placebo in 33,253
patients with varied medical conditions
● primary medical conditions included severe infections, lung diseases, traumatic injuries, and
prevention of bronchopulmonary dysplasia in premature infants
● corticosteroids included dexamethasone (55 trials), prednisolone (30 trials),
methylprednisolone (29 trials), prednisone (22 trials), hydrocortisone (16 trials), and other
steroids or combinations (7 trials)
– median duration of treatment was 8.5 days and median follow-up period was 56 days
– 85% of studies described use of concomitant medications including 19 studies with 2,379
patients in which NSAID use or nonuse was documented; overall analysis adjusted for use of
concomitant medications
– adverse e ects were described as any form of bleeding in 59 trials (upper/lower, minor,
hematemesis, melena, visible/occult blood in stool), perforation in 7 trials (perforated gastric
ulcer, ileum perforation), and bleeding and perforation in 6 trials
– 804 (2.4%) had gastrointestinal bleeding or perforation
– corticosteroids associated with increased risk of gastrointestinal bleeding or perforation in
subgroup analysis of 103 trials with 24,602 hospitalized patients (odds ratio 1.42, 95% CI 1.22-
1.66)
– no signi cant di erence in risk of gastrointestinal bleeding or perforation associated with
corticosteroids in subgroup analyses of
● 56 trials with 8,651 ambulatory patients
● 53 trials with 7,493 patients without peptic ulcer disease
● 19 trials with 2,379 patients who also took NSAIDs
● 14 trials with 1,494 patients who also took gastroprotective medications such as proton
pump inhibitors
– Reference - BMJ Open 2014 May 15;4(5):e004587 full-text

STUDY
⚬ SUMMARY
 spironolactone may be associated with increased risk for gastroduodenal ulcers or upper
gastrointestinal bleeding

CASE-CONTROL STUDY: BMJ 2006 Aug 12;333(7563):330 | Full Text

Details
– based on case-control study
– 523 cases of gastric or duodenal ulcer or upper gastrointestinal bleeding compared to 5,230
matched controls in the Netherlands
– current spironolactone use associated with increased risk of upper gastrointestinal bleeding or
gastroduodenal ulcer (odds ratio 2.7, 95% CI 1.2-6)
– Reference - BMJ 2006 Aug 12;333(7563):330 full-text , commentary can be found in BMJ
2006 Sep 2;333(7566):500 full-text

Helicobacter pylori infection

STUDY
● SUMMARY
association of H. pylori infection and risk of upper gastrointestinal bleeding among aspirin users
is uncertain

SYSTEMATIC REVIEW: Aliment Pharmacol Ther 2010 Oct;32(7):831 | Full Text

Details
⚬ based on systematic review with limited evidence
⚬ systematic review of 13 studies evaluating in uence of H. pylori on upper gastrointestinal bleeding
risk in patients taking aspirin
⚬ H. pylori associated with increased risk of upper gastrointestinal bleeding in patients taking aspirin
in 1 case-control study with 245 patients (summarized below)
⚬ data in 10 cohort studies did not allow for comparative testing and results of 2 randomized trials
were equivocal
⚬ Reference - Aliment Pharmacol Ther 2010 Oct;32(7):831 full-text
⚬ H. pylori infection associated with increased risk of bleeding in aspirin users

– based on case-control study of 98 patients with upper gastrointestinal bleeding taking low-dose
aspirin compared to 147 patients taking low-dose aspirin without gastrointestinal bleeding
– H. pylori infection associated with increased risk factor of upper gastrointestinal bleeding (odds
ratio 4.7, 95% CI 2-10.9)
– Reference - Aliment Pharmacol Ther 2002 Apr;16(4):779 full-text

STUDY
● SUMMARY
H. pylori infection may increase risk of bleeding among NSAID users

CASE-CONTROL STUDY: Gastroenterology 1999 Jun;116(6):1305

CASE-CONTROL STUDY: Am J Med 2004 May 1;116(9):601 | Full Text

Details
⚬ based on 2 case-control studies
⚬ 132 cases of bleeding peptic ulcers or hemorrhagic gastritis among patients taking NSAID at least
once in previous week compared to 136 NSAID users without gastrointestinal complications
– H. pylori diagnosed with serology or urea breath test in 57% cases vs. 43% controls
 – Reference - Gastroenterology 1999 Jun;116(6):1305

⚬ 80 cases of gastrointestinal bleeding compared to 80 controls without bleeding

– H. pylori detected in 79% vs. 56% (p = 0.004)

– Reference - Am J Med 2004 May 1;116(9):601 full-text

Differential Diagnosis

Causes

● most common causes of nonvariceal upper gastrointestinal (GI) bleeding include 5

⚬ peptic ulcer disease (20%-50%)

⚬ gastroduodenal erosions (8%-15%)
⚬ Mallory-Weiss tear (8%-15%)
⚬ erosive esophagitis (5%-15%)
⚬ gastrointestinal angiodysplasias/gastric antral vascular ectasias (5%)
⚬ upper gastrointestinal tumors (5%)
⚬ Dieulafoy's lesion (dilated tortuous submucosal arteries projecting into mucosa) (rare)

● causes of upper GI bleeding in cohort of 258 adults hospitalized for acute upper gastrointestinal
bleeding in San Diego, California health maintenance organization in 1991
⚬ peptic ulcer in 62% (mostly duodenal ulcer or gastric ulcer)

IMAGE 1 OF 2

Active Arterial Bleeding

Active arterial spurting (dotted arrow) from a duodenal

ulcer (solid ulcer). This lesion is at the highest risk for
rebleeding and must be treated endoscopically, with
interventional radiology, or surgery if bleeding persists.

⚬ stress-related (erosive) mucosal disease in 14% (esophagitis)

⚬ esophageal varices in 6%
⚬ Mallory-Weiss tear in 3.5%
⚬ esophageal ulcer in 4 patients (1.6%)
⚬ malignancy in 4 patients (1.6%)
⚬ Dieulafoy's lesion in 3 patients (1.2%)
⚬ iatrogenic esophageal laceration in 2 patients
⚬ single cases of paraesophageal hernia, radiation esophagitis, gastric vascular malformation
⚬ unknown in 8%
⚬ Reference - Am J Gastroenterol 1995 Feb;90(2):206

● duodenal ulcer, gastric ulcer, and esophageal varices were most common ndings on upper
endoscopy in retrospective cohort of 2,267 endoscopies for upper gastrointestinal bleeding in 139
military medical facilities (Am J Gastroenterol 1995 Apr;90(4):568 )
● acute esophageal necrosis

⚬ may present with either hematesis or melena

⚬ estimated incidence 0.01-0.28% among patients receiving esophagogastroduodenosocpy
⚬ characterized by black distal esophagus on endoscopy that becomes abruptly normal at
gastroesophageal juncture though may have some proximal involvement
⚬ patients often have malnutrition, gastric outlet obstruction and multiple comorbidities such as
atherosclerosis, diabetes, malignancy, or alcohol dependence
⚬ treatment is supportive care including nutritional support, intravenous uids, and antacids
⚬ perforation and strictures are potential complications
⚬ mortality attributable to acute esophageal necrosis 6%
⚬ Reference -Ann Gastroenterol 2019 Nov;32(6):529 full-text

● causes of occult gastrointestinal bleeding originating from upper gastrointestinal tract

⚬ esophagus

– erosive esophagitis (common)

– gastroesophageal varices (more likely to present as massive acute bleeding)
– Dieulafoy's lesion
– Mallory-Weiss syndrome (Eur J Intern Med 2012 Jun;23(4):e92 )
– malignancy (Aliment Pharmacol Ther 2013 Jul;38(2):144 full-text )
– acute esophageal necrosis (Ann Gastroenterol 2019 Nov;32(6):529 full-text )
⚬ stomach

– gastric ulcer
– erosive gastritis (common)
– gastric antral vascular ectasia (GAVE, or "watermelon" stomach) (Dig Liver Dis 2011
May;43(5):345 )
– gastrointestinal angiodysplasia
– Cameron erosions within hiatal hernia
– portal gastropathy

⚬ small intestine (duodenum)

– duodenitis or duodenal ulcer

– Dieulafoy's lesion
– gastrointestinal angiodysplasia
– celiac disease
– Crohn disease
– malignancy (Aliment Pharmacol Ther 2013 Jul;38(2):144 full-text )
⚬ other

– malignancy
– vasculitis
– aortoenteric stula
– large polyps
– hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu syndrome)
– blue rubber bleb nevus syndrome
– amyloidosis
– hemangioma
– radiation-induced mucosal injury
– hemobilia (Gastrointest Endosc Clin N Am 2015 Jul;25(3):583 )
⚬ Reference - Am Fam Physician 2004 Feb 15;69(4):875 full-text
● skin diseases that may have gastrointestinal involvement include

⚬ melanoma with metastasis

⚬ blue rubber bleb nevus syndrome
⚬ Kaposi sarcoma
⚬ visceral neuro bromatosis (Recklinghausen disease)
⚬ pseudoxanthoma elasticum
⚬ Reference - CMAJ 2006 Sep 12;175(6):583 full-text

● upper gastrointestinal bleeding due to aortoduodenal stula in 2 case presentations (N Engl J Med
2013 Feb 7;368(6):562 ) and (BMJ Case Rep 2013 Mar 13;2013 )

● upper gastrointestinal bleeding due to metastatic renal cell carcinoma in 2 men in case report (BMC
Gastroenterol 2007 Jan 31;7:4 full-text )

Mimics

● acute lower gastrointestinal bleeding 5

● acute variceal hemorrhage

● other blood loss or false-positive testing

⚬ extra-intestinal blood loss

– epistaxis (nosebleed)
– gingival bleeding
– tonsillitis/pharyngitis
– hemoptysis

⚬ false-positive fecal occult blood test

– red meat consumption

– consumption of fruits such as cantaloupe, grapefruit, and gs
– consumption of certain uncooked vegetables such as radish, cauli ower, broccoli, turnip,
horseradish
⚬ Reference - Am Fam Physician 2004 Feb 15;69(4):875 full-text

History and Physical

History

Chief concern (CC)

● gastrointestinal (GI) bleeding may present with 3 , 5

⚬ hematemesis - vomiting of fresh blood

⚬ co ee ground emesis - vomiting of altered black blood
⚬ melena - black tarry stools
⚬ hematochezia - red blood via rectum (usually from lower GI tract but sometimes from brisk
bleeding in upper GI tract)

● lightheadedness, weakness, tachycardia, cold hands and feet due to hypovolemia or iron de ciency
anemia
STUDY
● SUMMARY
most predictive findings to diagnose acute upper gastrointestinal bleeding appear to be melena
on exam, history of upper GI bleed, and positive nasogastric lavage, while syncope, cirrhosis,
malignancy, low hemoglobin, and elevated pulse may predict severe bleed DynaMed Level 2

SYSTEMATIC REVIEW: JAMA 2012 Mar 14;307(10):1072

Details
⚬ based on systematic review of studies with methodologic limitations
⚬ systematic review of 8 diagnostic cohort studies evaluating historical features, symptoms, signs,
bedside maneuvers, and laboratory tests for distinguishing acute upper GI bleeding from acute
lower GI bleeding in adults admitted for or presenting to emergency department with GI bleed
⚬ only 1 of 8 studies classi ed as level 1 quality (prospective study with > 200 patients and blinded
clinical evaluation with reference standard) and this study did not contribute to results
⚬ factors which may help diagnose acute upper GI bleeding (positive likelihood ratio > 5)

Table 1. Factors Suggesting Upper GI Bleeding

Finding Sensitivity Speci city Positive Number of

Likelihood Studies
Ratio

History of 22% 96% 6.2 (95% CI 1

upper GI 2.8-14)
bleeding

History of Range Range Range 5.1- 2

black stool 77%-95% 81%-87% 5.9
(melena)

Melenic 49% 98% 25 (95% CI 4- 1

stool on 174)
exam

Nasogastric 44% 95% 9.6 (95% CI 1

lavage with 4-23)
blood or
co ee
grounds
 Finding Sensitivity Speci city Positive Number of
Likelihood Studies
Ratio

Blood urea 51% 93% 7.5 (95% CI 6

nitrogen/cre 2.8-12)
atinine ratio
≥ 30

Abbreviations: GI, gastrointestinal.

⚬ factors suggesting more serious upper GI bleeding needing urgent endoscopy

Table 2. Factors of Severity of Bleeding

Clinical Sensitivity Speci city Positive Number of

Factors Likelihood Studies
Ratio

History of 22% 94% 3.7 (95% CI 1

malignancy 1.6-8.8)
or cirrhosis

Syncope 8% 98% 3 (95% CI 1

1.7-5.4)

Pulse > 60%-79% 82%-89% 4.9 (95% CI 1

100/minute 3.2-7.6)

Nasogastric 77% 76% 3.1 (95% CI 4 studies (3

lavage of red 1.2-14) studies
blood limited by
signi cant
heterogeneit
y)

Hemoglobin 65%-68% 86%-89% 4.5-6.2 2

< 8 g/dL
 Clinical Sensitivity Speci city Positive Number of
Factors Likelihood Studies
Ratio

Serum urea 63% 83% 3.6 (95% CI 1

nitrogen 2.4-5.5)
level

White blood 61% 82% 3.4 (95% CI 1

cell count 2.2-5.1)

⚬ Reference - JAMA 2012 Mar 14;307(10):1072

History of present illness (HPI)

● suggestive ndings by underlying cause of bleeding may include 3

⚬ peptic ulcer disease, gastritis, or duodenitis - nighttime pain, pain reduction with food intake
⚬ esophagitis or esophageal ulcer - heartburn, indigestion, dysphagia
⚬ Mallory-Weiss tear - bleeding episode preceded by retching, vomiting, or seizure
⚬ gastrointestinal malignancy - abdominal pain, weight loss
⚬ arteriovenous malformation - older age (> 70 years) with painless bleeding
⚬ Dieulafoy's lesion - painless bleeding (more common in men)

Medication history

● ask about 3 , 5

⚬ antiplatelet medications such as aspirin and other nonsteroidal anti-in ammatory drugs (NSAIDs)
⚬ anticoagulants such as warfarin and direct oral anticoagulants (DOACs [also called NOACs])
⚬ other medications that may increase risk of gastrointestinal bleeding (for example, steroids or
selective serotonin reuptake inhibitor [SSRIs])

● also ask about iron supplementation, which can turn the stool color black (Lancet 2016 Feb
27;387(10021):907 )

Past medical history (PMH)

● ask about history of gastrointestinal disease or bleeding 3

● ask about evaluation for Helicobacter pylori infection if patient has history of peptic ulcer disease 3

● history suggestive of underlying cause of bleeding may include 3

⚬ peptic ulcer disease

⚬ gastritis or duodenitis
⚬ Helicobacter pylori infection
⚬ gastrointestinal angiodysplasia
⚬ iron de ciency anemia
⚬ previous abdominal operations
Social history (SH)

● ask about alcohol, tobacco, or illicit drug use 3

Physical

General physical

● evaluate volume status - ndings in adults with hypovolemia may include (signs may be masked or
absent in older adults)
⚬ dry mucous membranes
⚬ sunken-appearing eyes
⚬ increased capillary re ll time (normal is 1-3 seconds)
⚬ decreased skin turgor
⚬ hypotension
⚬ orthostatic changes
⚬ tachycardia
⚬ weak and thready peripheral pulses
⚬ at neck veins in supine position
⚬ oliguria
⚬ functional signs of dehydration (change in mental status or falls)
⚬ see Dehydration and Hypovolemia in Adults for details

● assess for weight loss and cachexia, which may suggest malignancy 3

Skin

● telangiectasias (especially face, tongue, and vermillion border of lips) (Am J Gastroenterol 2000
Feb;95(2):415 )

● assess for signs of liver disease and/or portal hypertension, which may suggest esophageal varices as
source of bleeding, for example
⚬ jaundice
⚬ distended abdominal veins (caput medusae)
⚬ spider angiomata
⚬ palmar erythema
⚬ see also Portal Hypertension and Acute Variceal Hemorrhage

HEENT

● pigmentation (small black or brown dark spots) of lips and buccal mucosa may occur with Peutz-
Jeghers syndrome (hamartomatous polyposis)

● look for extra-intestinal sources of bleeding such as nasopharyngeal bleeding, tonsillitis/pharyngitis,

or gingival bleeding (Am Fam Physician 2004 Feb 15;69(4):875 full-text )

Neck

● left supraclavicular adenopathy (Virchow node) may suggest gastric carcinoma

Cardiac

● assess for murmurs, for example gastrointestinal angiodysplasia may be associated with aortic
stenosis (crescendo-decrescendo systolic ejection murmur)
Abdomen

● signs of portal hypertension such as ascites, hepatomegaly, or splenomegaly may suggest esophageal

varices as source of bleeding 3

● palpable mass may indicate gastrointestinal malignancy (ISRN Surg 2011;2011:894829 full-text )

Rectal

● evaluate stools for melena, bright red blood, or occult blood 3

Management (Evaluation and Treatment)

Management overview

● initial resuscitation and assessment

⚬ assess hemodynamic status and begin resuscitative measures as needed (ACG Strong
recommendation; ESGE Strong recommendation, Moderate-quality evidence)
– prompt uid replacement with crystalloid IV uids
– consider blood transfusion for hemoglobin < 7 g/dL

⚬ use a validated risk assessment scale, such as Rockall or Blatchford score to inform timing of
endoscopy, time of discharge, and level of care (ACG Conditional recommendation; ESGE Strong
recommendation, Moderate-quality evidence)
⚬ consider discharge from emergency department without inpatient endoscopy for patients with all
of following (equivalent to a Blatchford score of 0) (ACG Conditional recommendation; ESGE Strong
recommendation, Moderate-quality evidence) or with Blatchford score of 1 (ESGE Strong
recommendation, Moderate-quality evidence or with Blatchford score of ≤ 1 (ICUGB Conditional
recommendation, Low-quality evidence)
– urea nitrogen < 18.2 mg/dL
– hemoglobin ≥ 13 g/dL for men (12 g/dL for women)
– systolic blood pressure ≥ 110 mm Hg
– pulse < 100 beats/minute
– absence of melena, syncope, cardiac failure, and liver disease

⚬ routine nasogastric or orogastric lavage not recommended (ESGE Strong recommendation,

Moderate-quality evidence), and is not required (ACG Conditional recommendation)
– blood or co ee-ground-like material identi es likelihood of upper gastrointestinal bleeding and
may suggest high-risk lesion
– negative nasogastric aspiration may not be accurate for ruling out upper gastrointestinal
bleeding in patients with hematochezia or melena but without hematemesis DynaMed Level 2

● use proton pump inhibitor (PPI) before endoscopy to decrease likelihood of higher risk stigmata of
hemorrhage at endoscopy (ACG Conditional recommendation; ESGE Strong recommendation, High-
quality evidence), but do not delay endoscopy (ESGE Strong recommendation, High-quality evidence;
ICUGB Grade 1B)

● endoscopy

⚬ obtain esophagogastroduodenoscopy (EGD) within 24 hours if possible, and within 12 hours if

high-risk clinical features (such as tachycardia, hypotension, bloody emesis, or bloody nasogastric
aspirate in hospital) (ACG Conditional recommendation; ESGE Strong recommendation, Moderate-
quality evidence)
 ⚬ early endoscopy appears safe and may reduce duration of hospitalization compared to delayed
endoscopy in patients with nonvariceal upper gastrointestinal bleeding DynaMed Level 2

● for peptic ulcer, consider endoscopic treatment for high-risk stigmata (active bleeding, visible vessel,
adherent clot resistant to irrigation)
⚬ endoscopic therapy should not be given to patients who have an ulcer with a clean base or a at
pigmented spot (ACG Strong recommendation; ESGE Strong recommendation, Moderate-quality
evidence)
⚬ options include epinephrine injection (should not be used alone), thermocoagulation, injection of
sclerosant, and mechanical hemostasis (clips)
⚬ addition of second endoscopic method (sclerosing agent, mechanical hemostasis, or thermal
device) after epinephrine injection may reduce further bleeding and surgery in patients with major
hemorrhage from peptic ulcers DynaMed Level 2

● after successful endoscopic hemostasis of ulcer disease

⚬ start high-dose proton pump inhibitor (PPI) (such as omeprazole or pantoprazole 80 mg IV bolus
followed by 8 mg/hour continuous infusion for 72 hours) in patients with high-risk stigmata (ACG
Strong recommendation; ICUGB Strong recommendation, Moderate-quality evidence; ESGE Strong
recommendation, High-quality evidence)
⚬ patients with high-risk stigmata should generally be hospitalized for 3 days assuming no
rebleeding and no other reason for hospitalization; clear liquids may be taken soon after
endoscopy (ACG Conditional recommendation)

● test all patients with peptic ulcer for Helicobacter pylori infection and treat if positive (ACG Strong
recommendation; ESGE Strong recommendation, Low-quality evidence; ICUGB Grade 1A)

● if rebleeding or uncontrolled bleeding, consider repeat endoscopic therapy, selective arterial

embolization, or surgery

● for erosive esophagitis, continue PPI therapy, and see also Gastroesophageal Re ux Disease (GERD)

● if no bleeding source identi ed on EGD, consider evaluation for obscure bleeding

● for treatment of acute varices, see Acute Variceal Hemorrhage - Treatment

Resuscitation

General information

● assess hemodynamic status immediately and begin resuscitative measures as needed (ACG Strong

recommendation; ESGE Strong recommendation, Moderate-quality evidence) 4 , 6

● colloid or crystalloid may be used to achieve volume restoration prior to giving blood products (SIGN

Grade B) 1

● uids should be titrated carefully even in context of uid responsiveness, and especially in presence
of elevated intravascular lling pressures or extravascular lung water (Intensive Care Med 2014
Dec;40(12):1795 full-text , commentary can be found in Intensive Care Med 2015 Mar;41(3):570
)

Blood transfusions
● recommendations on restrictive threshold for transfusion vary

⚬ target of hemoglobin ≥ 7 g/dL suggested by American College of Gastroenterology (ACG

Conditional recommendation) 4
⚬ target between 7 g/dL and 9 g/dL recommended by European Society of Gastroentrology (ESGE

Strong recommendation, Moderate-quality evidence) 6

⚬ target modi ed to 8 g/dL from previously advised 7 g/dL by International Consensus Group ( Ann
Intern Med 2019 Dec 3;171(11):805 full-text )

CLINICIANS' PRACTICE POINT

While the exact threshold for initiating transfusion in patients with nonvariceal upper
gastrointestinal bleeding varies among expert consensus opinion, clinical judgement regarding
hemodynamic stability, rate of bleeding, likely hemoglobin dilution with crystalloid infusion, and
comorbidities ultimately informs the decision to transfuse.

● consider higher hemoglobin target if

⚬ clinical evidence of intravascular volume depletion (such as hypotension and tachycardia) or

comorbidities (such as coronary artery disease) (ACG Conditional recommendation; ICUGB
Conditional recommendation, Very low-quality evidence; ESGE Strong recommendation, Moderate-
quality evidence) 2 , 4 , 6
⚬ high suspicion of vigorous active ongoing bleeding or an uncorrected coagulopathy exists 6

STUDY
● SUMMARY
restrictive red blood cell transfusion threshold may reduce mortality compared to liberal
threshold in patients with upper gastrointestinal bleeding DynaMed Level 2

COCHRANE REVIEW: Cochrane Database Syst Rev 2016 Oct 12;(10):CD002042

Details
⚬ based on Cochrane review limited by clinical heterogeneity
⚬ systematic review of 31 randomized trials comparing restrictive vs. liberal transfusion threshold in
12,587 patients having red blood cell transfusion for any condition
⚬ 3 trials enrolled patients with upper gastrointestinal bleeding
⚬ trials varied in de nitions of restrictive and liberal transfusion threshold and use of initial red blood
cell transfusion
⚬ in patients with upper gastrointestinal bleeding, restrictive transfusion threshold associated with

– reduced 30-day mortality in analysis of 3 trials with 1,522 patients

● risk ratio 0.65 (95% CI 0.43-0.97)

● NNT 25-477 with 30-day mortality 7% in liberal transfusion threshold group

– reduced need for red blood cell transfusion in 3 trials with 1,875 patients

⚬ Reference - Cochrane Database Syst Rev 2016 Oct 12;(10):CD002042

⚬ using red blood cell transfusion threshold of hemoglobin < 7 g/dL reduces mortality
compared to threshold of hemoglobin < 9 g/dL in adults with severe acute upper
gastrointestinal bleeding
 DynaMed Level 1

– based on randomized trial

– 921 adults > 18 years old with severe acute upper gastrointestinal bleeding (49% with peptic
ulcer, 21% with esophageal varices) were randomized to 1 of 2 thresholds for red blood cell
transfusion and followed for 45 days
● transfusion when hemoglobin (Hb) < 7 g/dL with target range 7-9 g/dL (restrictive strategy)
● transfusion when Hb < 9 g/dL with target range 9-11 g/dL (liberal strategy)

– exclusion criteria included exsanguinating bleeding, low risk of rebleeding, acute coronary
syndrome, symptomatic peripheral vasculopathy, stroke, and transfusion in last 90 days
– all patients transfused with 1 unit of red blood cells followed by additional unit if Hb below
target range
– 889 patients (96.5%) were included in analysis (32 excluded for ineligibility, major protocol
violations, or withdrawal)
– comparing restrictive vs. liberal transfusion strategy

● all-cause mortality 5% vs. 9% (p = 0.02, NNT 25)

● death due to uncontrolled bleeding in 0.7% vs. 3.1% (p = 0.01, NNT 42)
● further bleeding in 10% vs. 16% (p = 0.01, NNT 17)
● adverse events in 40% vs. 48% (p = 0.02, NNT 13)
● serious adverse events in 12% vs. 18% (p = 0.01, NNT 17)
● no red blood cell transfusions in 51% vs. 15% (p < 0.001, NNT 3)

– Reference - N Engl J Med 2013 Jan 3;368(1):11 , correction can be found in N Engl J Med 2013
Jun 13;368(24):2341, editorial can be found in N Engl J Med 2013 Jan 3;368(1):75 ,
commentaries can be found in Hepatology 2014 Jul;60(1):422 , J Hepatol 2014 Feb;60(2):453
, J Fam Pract 2013 Sep;62(9):E6 , N Engl J Med 2013 Apr 4;368(14):1362 , Ann Intern Med
2013 Mar 19;158(6):JC6 , Nat Rev Gastroenterol Hepatol 2013 Feb;10(2):66

STUDY
● SUMMARY
red blood cell transfusion may not affect mortality but might increase rebleeding in adults with
upper gastrointestinal (GI) hemorrhage DynaMed Level 2

COCHRANE REVIEW: Cochrane Database Syst Rev 2010 Sep 8;(9):CD006613

Details
⚬ based on Cochrane review of trials with methodologic limitations
⚬ systematic review of 3 low-quality trials evaluating e cacy of red blood cell transfusion in 126
hemodynamically stable or unstable adults with upper GI hemorrhage
⚬ trial limitations included

– largest trial included less than half the adults in the nal analysis
– undetermined allocation concealment and blinding
– complete data available for 93 patients but underpowered to detect signi cant di erences
between groups
⚬ no signi cant di erences between groups in mortality risk found but wide con dence intervals
cannot rule out possible bene t or harm
⚬ rebleeding in 37.5% of transfusion group vs. 3.8% with no transfusion in 1 trial with 50 patients (p =
0.025)
⚬ Reference - Cochrane Database Syst Rev 2010 Sep 8;(9):CD006613
● see also Blood Products Administration

Assessment

Blood tests

● blood tests include 3

⚬ hematocrit and hemoglobin levels

⚬ platelet count
⚬ blood urea nitrogen (BUN)
⚬ creatinine
⚬ liver function tests
⚬ coagulation studies (prothrombin time [PT]/INR, partial thromboplastin time [PTT])

● upper gastrointestinal (GI) bleed may cause BUN/creatinine ratio > 30 (JAMA 2012 Mar
14;307(10):1072 )

● PT/INR may be elevated in cirrhosis of the liver due to impaired synthesis

Risk scoring tools to guide management

General information

● risk strati cation (based on clinical, laboratory, and endoscopic ndings) helps identify high risk
patients in need of close monitoring who may bene t from early interventions and low risk patients
who may be safely discharged 5

● stratify patients with validated prognostic scales into higher and lower risk categories to aid in
decisions such as timing of endoscopy, time of discharge, and level of care (ACG Conditional
recommendation; ESGE Strong recommendation, Moderate-quality evidence) 2 , 4 , 6
⚬ some scales incorporate endoscopic ndings into nal risk prediction 2 )

⚬ Rockall score or Glasgow Blatchford score (GBS) often recommended for pre-endoscopic decision-
making; GBS and initial (pre-endoscopic) Rockall score do not include endoscopic ndings, but full
Rockall score does

● patients with Glasgow Blatchford score of 0 (ACG Conditional recommendation; ESGE Strong
recommendation, Moderate-quality evidence) or 1 (ESGE Strong recommendation, Moderate-quality
evidence) or ≤ 1 (ICUGB Conditional recommendation, Low-quality evidence ) may be considered for
discharge from emergency department without inpatient endoscopy (advise patients of risk of
recurrent bleeding); score 0 or 1 includes all or most of the following 2 , 4 , 6
⚬ urea nitrogen < 18.2 mg/dL (or < 6.5 mmol/L)
⚬ hemoglobin ≥ 13 g/dL for men (12 g/dL for women)
⚬ systolic blood pressure ≥ 110 mm Hg
⚬ pulse < 100 beats/minute
⚬ absence of melena, syncope, cardiac failure, and liver disease

● Scottish Intercollegiate Guidelines Network (SIGN) recommendations 1

⚬ calculate initial (pre-endoscopic) Rockall score; patients with Rockall score 0 (< 60 years old without
hypotension, tachycardia, or comorbidity) should be considered for nonadmission or early
discharge with outpatient follow-up (SIGN Grade D)
 ⚬ endoscopy recommended if Rockall score > 0 (SIGN Grade D)
⚬ patients with full (postendoscopic) Rockall score < 3 should be considered for early discharge with
outpatient follow-up (SIGN Grade D)
⚬ patients with acute upper gastrointestinal hemorrhage should be admitted, assessed, and
managed in dedicated gastrointestinal bleeding unit (SIGN Grade D)

● review of upper gastrointestinal bleeding risk scores can be found in World J Gastrointest
Pathophysiol 2016 Feb 15;7(1):86 full-text

Rockall score

● see DynaMed calculator for Rockall Score for Upper Gastrointestinal Bleeding

● Rockall score predicts mortality based on 3 clinical features and 2 endoscopic criteria

⚬ derived from 4,185 British patients > 16 years old hospitalized with acute upper gastrointestinal
hemorrhage who had endoscopy (Gut 1996 Mar;38(3):316 PDF ) and validated in prospective
cohort of 951 Dutch patients with median age 71 years (Gut 1999 Mar;44(3):331 full-text )

Table 3. Initial (Pre-endoscopic) Rockall Scoring

0 1 2 3

Age < 60 years 60-79 years ≥ 80 years

Shock Systolic blood Systolic Systolic N/A

pressure ≥ blood blood
100 mm Hg, pressure ≥ pressure <
pulse < 100 100 mm Hg, 100 mm Hg
beats/minute pulse ≥ 100
beats/minut
e

Comorbidit No major N/A Cardiac Renal

y comorbidity failure, failure, liver
ischemic failure,
heart disseminate
disease, any d
major malignancy
comorbidity

Abbreviation: N/A, not applicable.

Table 4. Endoscopic Criteria for Rockall Scoring

 0 1 2

Diagnosis Mallory-Weiss All other Malignancy of

tear or no lesion diagnoses upper
identi ed gastrointestinal
tract

Major stigmata No stigmata of N/A Blood in upper

of recent recent gastrointestinal
hemorrhage hemorrhage, or tract, adherent
dark spot only clot, visible or
spurting vessel

Abbreviation: N/A, not applicable.

⚬ mortality risk (based on combined data of 2,131 patients from derivation and validation studies)

– 0.2% for score 0-2

– 6.8% for score 3-4
– 20% for score ≥ 5
– 43% for score ≥ 8

⚬ Reference - Am Fam Physician 2004 Dec 15;70(12):2348 full-text

● Scottish Intercollegiate Guidelines Network (SIGN) recommendations for use of Rockall score 1

⚬ calculate initial (pre-endoscopic) Rockall score in all patients with acute upper gastrointestinal
bleeding (SIGN Grade D)
– if Rockall score 0 (< 60 years old without hypotension, tachycardia, or comorbidity), consider
nonadmission or early discharge with outpatient follow-up
– if Rockall score > 0, endoscopy recommended

⚬ if full (postendoscopic) Rockall score < 3, consider early discharge with outpatient follow-up (SIGN
Grade D)

Glasgow Blatchford score

● Glasgow Blatchford score predicts need for acute intervention such as endoscopy, blood transfusion,
or surgery based on clinical and laboratory factors without endoscopic criteria

● see DynaMed calculator for Blatchford Score for Gastrointestinal Bleeding

STUDY
● SUMMARY
Glasgow Blatchford score = 0 rules out need for urgent intervention in patients with upper
gastrointestinal bleeding DynaMed Level 1

SYSTEMATIC REVIEW: JAMA 2012 Mar 14;307(10):1072

Details
⚬ based on systematic review
⚬ systematic review of 18 studies evaluating clinical prediction models for predicting severity of
upper GI bleeding
⚬ Blatchford score based on history and physical (nonendoscopic factors) and most extensively
validated

Table 5. Blatchford Score (0 if not listed)

Risk Factors Finding Points

BUN 18.2-22.4 mg/dL 2

22.4-28 mg/dL 4

28-70 mg/dL 5

≥ 70 mg/dL 6

Hemoglobin 12-13 g/dL in males 1

10-12 g/dL in males 3

10-12 g/dL in females 1

< 10 g/dL in males or 6

females

Systolic blood pressure 100-109 mm Hg 1

90-99 mm Hg 2

< 90 mm Hg 3

Pulse rate ≥ 100 beats/minute 1

Melena Present 1

Syncope Present 2

Hepatic disease Present 2

Heart failure Present 2

 Risk Factors Finding Points

Abbreviations: BUN, blood urea nitrogen.

⚬ pooled performance of Glasgow Blatchford score for predicting severity of upper GI bleeding

– using cuto score = 0 in analysis of 8 studies

● sensitivity 99.6% (95% CI 99%-100%)
● speci city 15% (95% CI 5%-25%)
● positive likelihood ratio 1.2 (95% CI 1-1.3)
● negative likelihood ratio 0.02 (95% CI 0-0.05)

– using cuto score ≤ 2 in analysis of 3 studies

● sensitivity 98% (95% CI 92%-99%)
● speci city 27% (95% CI 11%-53%)
● positive likelihood ratio 1.4 (95% CI 1.1-1.8)
● negative likelihood ratio 0.08 (95% CI 0.01-0.41)

⚬ Reference - JAMA 2012 Mar 14;307(10):1072

STUDY
● SUMMARY
Glasgow Blatchford score appears to have efficacy similar or may be superior to Rockall scores
for predicting transfusion need, need for intervention, and mortality after upper GI bleed
DynaMed Level 2

COHORT STUDY: Aliment Pharmacol Ther 2011 Aug;34(4):470

Details
⚬ based on cohort study with limited analysis reported
⚬ 1,555 patients with upper GI bleeding in 4 United Kingdom hospitals were evaluated
⚬ using area-under-the curve analysis (a continuous measure of score performance across the
continuum of scores)
– for predicting transfusion need, Glasgow Blatchford score (GBS) was superior to both initial and
full Rockall score (p < 0.0001 for both)
– for predicting need for endoscopic or surgical intervention, GBS was superior to initial Rockall
score (p < 0.0001) and similar to full Rockall score
– for mortality prediction, GBS was similar to initial Rockall score and full Rockall score

⚬ sensitivity, speci city, and predictive values for speci c score cuto s not reported
⚬ Reference - Aliment Pharmacol Ther 2011 Aug;34(4):470

Other clinical prediction rules

● other clinical prediction rules for nonvariceal upper gastrointestinal bleeding include

⚬ Cedars-Sinai Medical Center predictive index

⚬ Baylor College scoring system
⚬ Acute Physiology and Chronic Health Evaluation (APACHE) II score
⚬ Reference - Dig Liver Dis 2004 Apr;36(4):271

STUDY
● SUMMARY
Progetto Nazionale Emorragia Digestiva (PNED) score predicts 30-day mortality in patients with
nonvariceal upper gastrointestinal bleeding and appears more accurate than Rockall score
DynaMed Level 1

COHORT STUDY: Am J Gastroenterol 2010 Jun;105(6):1284

Details
⚬ based on validation cohort study
⚬ prospective validation cohort of 1,360 adults with nonvariceal upper gastrointestinal bleeding
independent from derivation cohort of 1,020 patients
⚬ characteristics of validation cohort

– peptic ulcers were cause of bleeding in 63%

– high-risk stigmata (active bleeding, visible vessels, and adherent clots) seen on endoscopy in
43%
– endoscopic treatment given in 57%
– proton pump inhibitors given in 88%

⚬ outcomes

– recurrent bleeding in 4%
– emergency surgery in 2.4%
– 30-day mortality 4.9%

⚬ PNED score (low-risk 0-4, medium-risk 5-8, high-risk > 8)

– 1 point assigned for each of

● American Society of Anesthesiology (ASA) class 3

● time to admission < 8 hours

– 2 points assigned for each of

● hemoglobin level ≤ 7 g/dL

● ≥ 80 years old
● renal failure

– 3 points assigned for each of

● rebleeding
● ASA class 4
● neoplasia
● liver cirrhosis

– 4 points assigned for failure of endoscopic treatment

⚬ 30-day mortality predicted by PNED risk score

– about 1% if PNED risk score 0-1

– about 4% if PNED risk score 2-4
– 10% if PNED risk score 5-8
– 32% if PNED risk score > 8 (positive likelihood ratio 16.05)

⚬ PNED risk score better than Rockall score for predicting mortality
⚬ Reference - Am J Gastroenterol 2010 Jun;105(6):1284

STUDY
● SUMMARY
AIMS65 bedside risk score predicts in-hospital mortality in patients with acute upper
gastrointestinal bleeding admitted to emergency department DynaMed Level 1

PREDICTION RULE: Gastrointest Endosc 2011 Dec;74(6):1215

 Details
⚬ based on prognostic cohort study with independent derivation and validation cohorts
⚬ derivation cohort included 29,222 patients with acute upper gastrointestinal bleeding admitted to
emergency department between 2004 and 2005
⚬ validation cohort included 32,504 similar patients admitted to emergency department between
2006 and 2007
⚬ bleeding source was nonvariceal in > 98% of patients in derivation and validation cohorts
⚬ in-hospital mortality was 3.2% in derivation cohort and 2.7% in validation cohort
⚬ bedside risk score (AIMS65) assigned 1 point for each risk factor associated with increased in-
hospital mortality in derivation cohort (total score 0-5)
– albumin levels < 3 mg/dL
– INR > 1.5
– altered mental status
– systolic blood pressure < 90 mm Hg
– > 65 years old

⚬ in-hospital mortality in derivation and validation cohorts by AIMS65 score

AIMS65 Score Derivation Cohort Validation Cohort

0 0.3% 0.3%

1 1.2% 1.2%

2 3.6% 2.8%

3 9.8% 8.5%

4 21.8% 15.1%

5 31.8% 24.5%

⚬ Reference - Gastrointest Endosc 2011 Dec;74(6):1215 , editorial can be found in Gastrointest

Endosc 2011 Dec;74(6):1225

STUDY
● SUMMARY
AIMS65 score appears less sensitive than Glasgow Blatchford score for stratifying higher- and
lower-risk patients presenting to emergency department with upper GI bleeding
DynaMed Level 2

COHORT STUDY: Acad Emerg Med 2015 Jan;22(1):22

Details
⚬ based on prognostic cohort study with unclear blinding of reference standard
⚬ 254 patients presenting to emergency department with upper GI bleeding from variceal or
nonvariceal sources were assessed by AIMS65 and Glasgow Blatchford scores
⚬ reference standard for classi cation as high risk was any of
 – need for endoscopic or surgical intervention to control bleeding
– need for blood transfusion
– rebleeding
– admission to intensive care unit
– death within 30 days

⚬ need for transfusion determined by treating physician (who were aware of data collection for
scoring), need for and timing of electroencephalography (EGD) determined by gastroenterologist
(unaware of data collection)
⚬ 59.8% were classi ed as high risk by reference standard
⚬ for prediction of high risk

– AIMS65 score with cuto > 0 had

● sensitivity 77.6%
● speci city 65.7%
● positive predictive value 77.1%
● negative predictive value 66.3%

– Glasgow Blatchford score with cuto ≥ 2 had

● sensitivity 97.4%
● speci city 43.1%
● positive predictive value 71.8%
● negative predictive value 91.7%

⚬ Glasgow Blatchford score ≥ 2 had better discrimination than AIMS65 score > 0 for predicting high
risk (p < 0.001)
⚬ Reference - Acad Emerg Med 2015 Jan;22(1):22

STUDY
● SUMMARY
clinical prediction rule based on endoscopic findings and clinical history stratifies risk of poor
outcomes in patients with upper gastrointestinal hemorrhage DynaMed Level 1

PREDICTION RULE: Arch Intern Med 2007 Jun 25;167(12):1291 | Full Text

Details
⚬ based on prognostic cohort study with independent derivation and validation cohorts
⚬ 391 patients (mean age 63 years, 99% male) admitted to 3 United States Veterans A airs hospitals
with acute upper gastrointestinal hemorrhage were assessed for poor outcomes
– poor outcome 1 de ned as any of

● major rebleeding (with presence of either hypotension or fall in hematocrit of > 4% in 24

hours)
● need for urgent surgery/advanced technique to control hemorrhage
● all-cause (in-hospital) death

– poor outcome 2 de ned as poor outcome 1 plus new or worsening comorbidity

⚬ 360 patients having esophagogastroduodenoscopy were included in analysis and randomly divided
into derivation (244 patients) and validation (116 patients) cohorts
⚬ 19% had poor outcome 1 and 21.3% had poor outcome 2 in derivation cohort
⚬ risk model developed from factors independently associated with increased risk of poor outcomes
in derivation cohort including
– stigmata of recent hemorrhage
– APACHE II score ≥ 11
 – esophageal varices
– unstable comorbidity at hospital admission (only used for poor outcome 2)

⚬ rates of poor outcomes by presence of risk factors in derivation and validation cohorts

Risk Group Poor Outcome 1 Poor Outcome 2

Derivation Validation Derivatio Validation

Cohort Cohort n Cohort Cohort

Low risk (0 factors) 1.1% 2.2% 4.8% 7.5%

Intermediate risk (1 5% 4.2% 16.7% 18.9%

factor)

High risk (≥ 2 25.5% 22.7% 46.5% 56.5%

factors)

⚬ Reference - Arch Intern Med 2007 Jun 25;167(12):1291 full-text

STUDY
● SUMMARY
6 clinical factors associated with increased 6-week mortality risk after acute upper
gastrointestinal bleeding in patients with cirrhosis DynaMed Level 2

COHORT STUDY: Am J Emerg Med 2010 Oct;28(8):884

Details
⚬ based on retrospective cohort without independent validation
⚬ 389 patients presenting at emergency department with acute upper gastrointestinal bleeding who
had previous diagnosis of cirrhosis were analyzed
⚬ 8.1% died within 6 weeks
⚬ factors at presentation of upper gastrointestinal bleed associated with increased risk of death

– male sex
– hypoxemia (de ned as peripheral oxygen saturation < 95%)
– hepatocellular carcinoma
– nonhepatocellular malignancy
– higher bilirubin level
– higher INR

⚬ Reference - Am J Emerg Med 2010 Oct;28(8):884

Comparative performance clinical prediction rules

STUDY
● SUMMARY
Glasgow Blatchford score with cutoff ≤ 1 may have best predictive performance compared to 4
other clinical risk scores for identifying patients presenting with evidence of upper
gastrointestinal bleeding who can be safely managed as outpatients DynaMed Level 2

PREDICTION RULE: BMJ 2017 Jan 4;356:i6432 | Full Text

Details
⚬ based on prognostic cohort study without independent validation
⚬ 3,012 patients (median age 65 years, 58% male) presenting to hospital with evidence of upper
gastrointestinal bleeding were assessed with 5 clinical risk scores including
– Glasgow Blatchford score
– AIMS65 bedside risk score
– initial (pre-endoscopic) Rockall score
– full Rockall score
– Progetto Nazionale Emorragia Digestiva (PNED) score

⚬ 95% had follow-up data for 30 days

⚬ 45% had composite outcome of hospital based intervention (red blood cell transfusion, endoscopic
treatment, interventional radiology, or surgery) or death within 30 days
⚬ median length of hospital stay was 3 days
⚬ performance of Glasgow Blatchford score with cuto ≤ 1 to predict 30-day survival without
hospital-based intervention
– sensitivity 98.6%
– speci city 34.6%
– positive predictive value 96.6%
– negative predictive value 56%

⚬ 83% had data available for calculation of all pre-endoscopic scores

⚬ incidence of hospital-based intervention or death in patients with low risk scores on prediction
models using pre-endoscopic data

Low-risk Cuto Number of Patients Rate of

Included in Analysis Composite
Outcome

Glasgow Blatchford score ≤ 1 564 3.4%

Initial Rockall score = 0 436 14%

AIMS65 score = 0 865 25%

⚬ performance of all 5 scores for prediction of composite outcome was calculated in 1,704 patients
(57%) with complete data for all scores and outcomes
– good discrimination with Glasgow Blatchford score (c-statistic 0.86) (p < 0.001 vs. all other
scores)
– modest discrimination with

● AIMS65 (c-statistic 0.68)

● initial Rockall score (c-statistic 0.66)
● full-Rockall score (c-statistic 0.7)
● PNED score (c-statistic 0.69)

– performance of Glasgow Blatchford score was consistent among centers (c-statistic 0.85-0.91),
but performance varied widely for AIMS65 score (c-statistic 0.54-0.75) and full Rockall score (c-
statistic 0.57-0.79)
⚬ scores with highest predictive performance for individual outcomes
 – Glasgow Blatchford score for prediction of need for endoscopic treatment (c-statistic 0.75)
– PNED and AIMS65 for prediction of mortality (c-statistic 0.77 for both)
– PNED for prediction of rebleeding (c-statistic 0.85)

⚬ Reference - BMJ 2017 Jan 4;356:i6432 full-text

Nasogastric aspiration

● nasogastric or orogastric lavage

⚬ not recommended routinely in patients with acute upper gastrointestinal bleeding (ESGE Strong

recommendation, Moderate-quality evidence) 6

⚬ commonly done for suspected upper gastrointestinal bleeding 3

⚬ placement is controversial 5

⚬ blood or co ee-ground-like material identi es likelihood of upper gastrointestinal bleeding and

may suggest high-risk lesion 4 , 5

⚬ clear or bile-stained aspirate may be associated with 18% false-negative rate 4

⚬ American College of Gastroenterology 2014 practice guidelines note nasogastric or orogastric

lavage is not required in patients with upper gastrointestinal bleeding for diagnosis, prognosis,
visualization, or therapeutic e ect (ACG Conditional recommendation) 4
⚬ consider endotracheal intubation prior to endoscopy to protect from potential aspiration in
patients with ongoing active hematemesis, encephalopathy, or agitation (ESGE Weak
recommendation, Low-quality evidence) 6

STUDY
● SUMMARY
negative nasogastric aspiration may not be accurate for ruling out upper gastrointestinal
bleeding in patients with hematochezia or melena but without hematemesis DynaMed Level 2

SYSTEMATIC REVIEW: Acad Emerg Med 2010 Feb;17(2):126 | Full Text

Details
⚬ based on systematic review of studies with methodologic limitations
⚬ systematic review of 3 retrospective studies with 511 patients with hematochezia or melena but
without hematemesis who had nasogastric aspiration (with or without lavage) and endoscopy
⚬ all 3 studies were limited by using a convenience sample (rather than consecutive sample) and/or
absence of blinding
⚬ prevalence of upper gastrointestinal bleeding ranged from 32% to 74%
⚬ predictive performance of nasogastric aspiration to detect upper gastrointestinal bleeding (ranges)

– sensitivity 42%-84%
– speci city 54%-91%
– positive predictive value 41%-93%
– positive likelihood ratio 1.44-4.74
– negative predictive value 61%-78%
– negative likelihood ratio 0.2-0.65

⚬ Reference - Acad Emerg Med 2010 Feb;17(2):126 full-text

STUDY
● SUMMARY
nasogastric lavage may have limited value in predicting high risk lesions in patients with upper
gastrointestinal tract bleeding DynaMed Level 2
 RANDOMIZED TRIAL: J Investig Med 2017 Apr;65(4):759

Details
⚬ based on randomized noninferiority trial with choice of noninferiority margin not explained
⚬ 280 patients (mean age 49 years, 65% male) with upper gastrointestinal tract bleeding were
randomized to nasogastric lavage vs. no nasogastric lavage
⚬ noninferiority of nasogastric lavage de ned as rate of ability to accurately predict presence of a
high risk lesion < 15% lower than no nasogastric lavage at limit of 95% CI for di erence
⚬ nasogastric tube could not be placed in 8%
⚬ prediction of high risk lesion in 38.8% with nasogastric lavage vs. 34.6% without nasogastric lavage
(95% CI -11.6% lower to 3.2% higher, noninferiority met)
⚬ no signi cant di erence in rebleeding or mortality between groups
⚬ Reference - J Investig Med 2017 Apr;65(4):759

STUDY
● SUMMARY
nasogastric lavage may reduce time to endoscopy in patients with upper gastrointestinal
bleeding DynaMed Level 2

COHORT STUDY: Gastrointest Endosc 2011 Nov;74(5):971

Details
⚬ based on retrospective cohort study
⚬ 632 patients (mean age 63 years, 98% male) with variceal and nonvariceal gastrointestinal bleeding
were included
⚬ propensity score was calculated based on time of presentation and clinical factors
⚬ 193 patients with nasogastric lavage and 193 propensity matched patients without nasogastric
lavage were analyzed
⚬ nasogastric lavage associated with

– earlier time to endoscopy (hazard ratio 1.49, 95% CI 1.09-2.04)

– decreased risk of 30-day mortality (odds ratio 0.84, 95% CI 0.37-1.92), not signi cant but CI
includes possibility of bene t or harm
⚬ endoscopy was performed within rst 10 hours of presentation in 75% with nasogastric lavage vs.
55% without nasogastric lavage (results estimated from graph)
⚬ no signi cant di erence in length of hospitalization, blood transfusion, or emergency surgery
between groups
⚬ Reference - Gastrointest Endosc 2011 Nov;74(5):971

● lidocaine may reduce patient discomfort during nasogastric tube placement

⚬ topical lidocaine may reduce pain of nasogastric tube placement, based on randomized placebo-
controlled trial in 40 adults (Ann Emerg Med 2000 May;35(5):421 )
⚬ nebulized lidocaine may reduce patient discomfort during nasogastric tube placement, but 17%
risk of nasal bleeding in randomized trial with 50 patients (Ann Emerg Med 2004 Aug;44(2):131 ),
commentary can be found in ACP J Club 2005 Jan-Feb;142(1):22 , Am Fam Physician 2005 May
1;71(9):1807

Medications

Proton pump inhibitors (PPIs)

● guideline recommendations for peptic ulcer disease 2 , 4 , 6

⚬ use pre-endoscopic PPI IV (80 mg bolus followed by 8 mg/hour infusion) to decrease likelihood of
higher risk stigmata of hemorrhage at endoscopy (ACG Conditional recommendation; ICUGB Grade
1B; ESGE Strong recommendation, High-quality evidence)
⚬ if endoscopy will be delayed or cannot be performed, PPI IV is recommended to reduce further
bleeding (ACG Conditional recommendation)
⚬ PPI treatment should not delay endoscopy (ESGE Strong recommendation, High-quality evidence;
ICUGB Grade 1B)
⚬ after successful endoscopic hemostasis, PPI IV with 80 mg bolus followed by 8 mg/hour continuous
infusion for 72 hours should be given to patients with high-risk stigmata (ulcer with active bleeding,
a nonbleeding visible vessel, or an adherent clot) (ACG Strong recommendation; ICUGB Strong
recommendation, Moderate-quality evidence; ESGE Strong recommendation, High-quality
evidence)
⚬ consider intermittent PPI IV (≥ 2 times daily) for 72 hours after endoscopy for patients receiving
hemostasis or with adherent clot not receiving hemostasis; high-dose oral PPI may be considered
in patients who can tolerate oral medication (ESGE Weak recommendation, Moderate-quality
evidence)
⚬ patients with ulcers that have at pigmented spots or clean bases can receive standard oral PPI
therapy once daily (ACG Strong recommendation)

● in patients with severe esophagitis (Los Angeles esophagitis classi cation Grade C or D, or stricture),
consider twice-daily standard PPI dosing to relieve symptoms, reduce acid exposure, and promote
healing (CAG Level 1B) (Can J Gastroenterol 2005 Jan;19(1):15 )

● pre-endoscopic treatment

STUDY
⚬ SUMMARY
PPI prior to endoscopy reduces need for endoscopic therapy during index endoscopy and
might reduce stigmata of recent hemorrhage, but does not reduce mortality or rebleeding
DynaMed Level 1

COCHRANE REVIEW: Cochrane Database Syst Rev 2010 Jul 7;(7):CD005415

Details
– based on Cochrane review
– systematic review of 6 randomized trials evaluating PPI vs. placebo, histamine-2 receptor
antagonist, or no treatment prior to endoscopy in 2,223 hospitalized patients with upper
gastrointestinal (GI) bleeding
– 1 high-quality trial excluded from analysis on stigmata of recent hemorrhage due to lack of data
for all randomized patients
– PPI associated with

● reduced stigmata of recent hemorrhage (active spurting or oozing, nonbleeding visible

vessel, or adherent clot) at index endoscopy in analysis of 4 trials with 1,332 patients (odds
ratio [OR] 0.67, 95% CI 0.54-0.84)
● reduced endoscopic therapy at index endoscopy in analysis of 3 trials with 1,983 patients (OR
0.68, 95% CI 0.5-0.93) (including 1 high-quality trial)
● no signi cant di erences at 30 days in

⚬ mortality in analysis of 6 trials with 2,223 patients (OR 1.12, 95% CI 0.72-1.73)
⚬ rebleeding in analysis of 5 trials with 2,121 patients (OR 0.81, 95% CI 0.61-1.09)
 ⚬ surgical intervention in analysis of 5 trials with 2,165 patients (OR 0.96, 95% CI 0.68-1.35)

– Reference - Cochrane Database Syst Rev 2010 Jul 7;(7):CD005415

– IV omeprazole prior to endoscopy in patients with upper gastrointestinal bleeding
reduces need for endoscopic therapy but does not reduce rate of recurrent bleeding or
30-day mortality
DynaMed Level 1

● based on randomized trial

● 638 patients with upper gastrointestinal bleeding randomized to omeprazole (80 mg IV bolus
followed by 8 mg/hour infusion) vs. placebo started prior to scheduled endoscopy the
following morning
● 7 patients were excluded from analysis - 3 withdrew before drug given, 4 were found not to
have upper gastrointestinal bleeding
● comparing omeprazole vs. placebo

⚬ need for endoscopic therapy in 19.1% vs. 28.4% (p = 0.007, NNT 11)
⚬ actively bleeding ulcers on endoscopy in 6.4% vs. 14.7% (p = 0.01, NNT 12)
⚬ among 377 patients with peptic ulcer bleeding need for endoscopic therapy in 22.5% vs.
36.8% (p = 0.002)
● no signi cant di erences in rates of

⚬ recurrent bleeding
⚬ need for blood transfusions
⚬ need for emergency surgery
⚬ death within 30 days

● Reference - N Engl J Med 2007 Apr 19;356(16):1631 full-text , commentary can be found
in N Engl J Med 2007 Jul 19;357(3):303 , ACP J Club 2007 Jul-Aug;147(1):18

● PPI after endoscopic treatment

STUDY
⚬ SUMMARY
intermittent PPI therapy may be as effective as continuous PPI therapy after endoscopy in
reduction of rebleeding in patients treated for upper gastrointestinal bleeding from ulcers
DynaMed Level 2

SYSTEMATIC REVIEW: JAMA Intern Med 2014 Nov 1;174(11):1755 | Full Text

Details
– based on systematic review of trials with methodologic limitations
– review of 10 trials with 1,373 patients with gastric or duodenal ulcers with active bleeding,
nonbleeding visible vessel, or adherent clot treated with endoscopic hemostasis and
randomized to intermittent PPI vs. continuous PPI
– all trials had ≥ 1 methodologic limitation including lack of blinding and allocation concealment
– intermittent PPI dosing varied in trials from 20 to 80 mg IV or orally once or twice daily, with or
without bolus
– continuous PPI was 80 mg IV bolus followed by 8 mg/hour IV for 72 hours
– prede ned margin of noninferiority was 3%
– rebleeding in 7 days (risk ratio 0.74, 95% CI 0.52-1.06) in analysis of 10 trials with 1,373 patients
– Reference - JAMA Intern Med 2014 Nov 1;174(11):1755 full-text , commentary can be found
in Ann Intern Med 2015 Jan 20;162(2):JC8
STUDY
⚬ SUMMARY
oral PPI therapy and IV PPI therapy after endoscopy associated with similar rebleeding rates
in patients treated for upper gastrointestinal ulcer bleeding DynaMed Level 2

SYSTEMATIC REVIEW: Br J Clin Pharmacol 2017 Aug;83(8):1619

Details
– based on systematic review of trials with methodologic limitations
– systematic review of 9 trials comparing oral proton pump inhibitor (PPI) therapy vs. PPI IV in
1,036 patients with bleeding peptic ulcer
● oral PPI was esomeprazole (2 trials), pantoprazole (2 trials), omeprazole (2 trials), rabeprazole
(1 trial), lansoprazole (1 trial), or one of omeprazole, pantoprazole, or rabeprazole (1 trial)
● IV PPI agent was esomeprazole (3 trials), omeprazole (2 trials), pantoprazole (3 trials), or one
of omeprazole, pantoprazole, or rabeprazole (1 trial)
● in PPI IV groups, IV therapy prescribed for rst 3 days, followed by oral PPI therapy for 1-2
months
– all trials had ≥ 1 limitation including

● no or unclear blinding of outcome assessors

● no or unclear blinding of participants
● unclear allocation concealment

– comparing oral PPI to IV PPI therapy, no signi cant di erence in

● rebleeding rate (odds ratio [OR] 0.93, 95% CI 0.6-1.46) in analysis of all trials, not signi cant
but CI includes possibility of bene t or harm
● 30-day mortality (odds ratio 0.89, 95% CI 0.27-2.93) in analysis of 7 trials with 705 patients,
not signi cant but CI includes possibility of bene t or harm
● need for surgery (OR 0.77, 95% CI 0.25-2.4) in analysis of 8 trials with 1,011 patients, not
signi cant but CI includes possibility of bene t or harm
● need for repeat endoscopy (OR 0.69, 95% CI 0.39-1.21) in analysis of 4 trials with 350
patients, not signi cant but CI includes possibility of bene t or harm
● mean volume of transfused blood in analysis of 6 trials with 615 patients
● mean length of hospital stay in analysis of 6 trials with 821 patients

– Reference - Br J Clin Pharmacol 2017 Aug;83(8):1619

STUDY
⚬ SUMMARY
oral PPI boluses after endoscopy may reduce risk of rebleeding requiring surgery compared to
continuous IV PPI drip but not compared to IV PPI boluses, while IV PPI drip and IV PPI
boluses may have similar clinical outcomes in patients with acute nonvariceal upper
gastrointestinal bleeding DynaMed Level 2

NETWORK META-ANALYSIS: J Clin Gastroenterol 2017 Sep;51(8):707

Details
– based on network meta-analysis limited by clinical heterogeneity
– systematic review and network meta-analysis of 39 randomized trials evaluating acid-
suppressive therapies in 7,767 patients endoscopically treated for acute nonvariceal upper
gastrointestinal bleeding
● PPI therapy categorized as PPI oral boluses (oral PPI), PPI IV bolus followed by continuous
infusion (IV PPI drip), and scheduled PPI IV boluses (IV PPI scheduled)
 ● studies compared IV PPI drip vs. oral PPI (6 trials), IV PPI drip vs. IV PPI scheduled (10 trials), IV
PPI drip vs. placebo (6 trials), IV PPI scheduled vs. IV H2 receptor antagonists (10 trials), IV PPI
drip vs. H2 antagonists (5 trials), and IV PPI scheduled vs. oral PPI (2 trials)
– network meta-analysis reported results with credibility intervals (CrI) instead of con dence
intervals due to inclusion of indirect comparisons
– studies varied in

● used PPI agent (omeprazole, rabeprazole, pantoprazole, lansoprazole, or esomeprazole)

● PPI dosage (standard or weight-based dosages)
● Forrest classi cations

– comparing oral PPI with IV PPI drip

● oral PPI associated with reduced rebleeding requiring surgery (risk ratio [RR] 0.3, 95% CrI 0.1-
0.78) in analysis of 5 trials
● no signi cant di erences in

⚬ mortality (RR 1.24, 95% CrI 0.31-4.99) in analysis of 5 trials, not signi cant but CI includes
possibility of bene t or harm
⚬ rebleeding within 72 hours (RR 1.16, 95% CrI 0.46-3.19) in analysis of 4 trials, not
signi cant but CrI includes possibility of bene t or harm
⚬ mean length of hospital stay in analysis of 5 trials
⚬ mean units of blood transfused in analysis of 5 trials

– comparing oral PPI with IV PPI scheduled, no signi cant di erences in

● mortality (RR 1.36, 95% CrI 0.34-5.78) in analysis of 2 trials, not signi cant but CrI includes
possibility of bene t or harm
● rebleeding within 72 hours (RR 1.15, 95% CrI 0.43-3.23) in 1 trial, not signi cant but CrI
includes possibility of bene t or harm
● rebleeding requiring surgery (RR 0.38, 95% CrI 0.09-2.07) in analysis of 2 trials, not signi cant
but CrI includes possibility of bene t or harm
● mean length of hospital stay in analysis of 2 trials
● mean units of blood transfused in 1 trial

– comparing IV PPI drip with IV PPI scheduled, no signi cant di erences in

● mortality (RR 1.11, 95% CrI 0.56-2.21) in analysis of 7 trials, not signi cant but CrI includes
possibility of bene t or harm
● rebleeding within 72 hours (RR 0.98, 95% CrI 0.48-1.95) in analysis of 3 trials, not signi cant
but CrI includes possibility of bene t or harm
● rebleeding requiring surgery (RR 1.27, 95% CrI 0.64-2.35) in analysis of 8 trials, not signi cant
but CrI includes possibility of bene t or harm
● mean length of hospital stay in analysis of 8 trials
● mean units of blood transfused in analysis of 5 trials

– Reference - J Clin Gastroenterol 2017 Sep;51(8):707

STUDY
⚬ SUMMARY
high-dose PPIs do not appear to be more effective for rebleeding and are associated with
similar mortality and surgical intervention rates compared to lower dose regimens for acute
peptic ulcer bleeding DynaMed Level 2

COCHRANE REVIEW: Cochrane Database Syst Rev 2013 Jun 12;(6):CD007999

Details
 – based on Cochrane review with statistical limitations
– systematic review of 22 randomized trials comparing di erent regimens of PPIs in patients with
acute peptic ulcer bleeding
– PPIs included omeprazole, pantoprazole, and lansoprazole
– high-dose de ned as cumulative dose ≥ 600 mg over rst 72 hours
– high-dose regimens associated with nonsigni cant increase in rebleeding (risk ratio 1.27, 95% CI
0.96-1.67) in analysis of 13 trials with 1,716 patients
– comparing high-dose regimens to low- or medium-dose regimens

● no signi cant di erences in

⚬ mortality (odds ratio 0.85, 95% CI 0.47-1.54) in analysis of 12 trials with 1,667 patients,
wide con dence intervals cannot exclude clinically relevant di erences
⚬ surgical intervention (risk ratio 1.33, 95% CI 0.63-2.77) in analysis of 9 trials with 1,270
patients, wide con dence intervals cannot exclude clinically relevant di erences
⚬ further endoscopic hemostatic treatment in analysis of 6 trials with 902 patients
⚬ blood transfusion in analysis of 6 trials with 1,069 patients

– Reference - Cochrane Database Syst Rev 2013 Jun 12;(6):CD007999

– similar results found in systematic review of 7 randomized trials (all included in Cochrane) (Arch
Intern Med 2010 May 10;170(9):751 , editorial can be found in Arch Intern Med 2010 May
10;170(9):747 , Arch Intern Med 2010 May 10;170(9):749 )

STUDY
⚬ SUMMARY
after 3-day esomeprazole infusion, esomeprazole 40 mg orally twice daily may reduce risk of
recurrent bleeding compared to esomeprazole 40 mg orally once daily in patients with peptic
ulcer bleeding and Rockall score ≥ 6 DynaMed Level 2

RANDOMIZED TRIAL: Gut 2014 Dec;63(12):1864

Details
– based on randomized trial without blinding
– 187 adults with peptic ulcer bleeding who had achieved endoscopic hemostasis were
randomized to esomeprazole 40 mg orally twice daily vs. esomeprazole 40 mg orally once daily
for 11 days
● all patients had 3-day esomeprazole infusion and Rockall score ≥ 6 prior to randomization
● after completing allocated treatment all patients received esomeprazole 40 mg orally once
daily for 2 weeks until end of 28-day study period
– comparing esomeprazole 40 mg orally twice daily vs. 40 mg orally once daily

● recurrent bleeding of peptic ulcer during days 4-14 in 9.7% vs. 23.4% (p = 0.01, NNT 8)
● recurrent bleeding of peptic ulcer during days 4-28 in 10.8% vs. 28.7% (p = 0.002, NNT 6)

– Reference - Gut 2014 Dec;63(12):1864

STUDY
⚬ SUMMARY
high-dose omeprazole decreases rebleeding risk compared to standard-dose omeprazole
following endoscopy for acute peptic ulcer bleeding DynaMed Level 1

RANDOMIZED TRIAL: Br J Surg 2011 May;98(5):640

Details
 – based on randomized trial
– 126 patients who had endoscopy for acute peptic ulcer bleeding were randomized to
omeprazole 80 mg IV bolus then 8 mg/hour infusion for 72 hours (high dose) vs. omeprazole 40
mg IV once daily for 3 days (standard dose)
– rebleeding in 2 patients (3%) with high-dose omeprazole vs. 10 patients (16%) with standard-
dose omeprazole (p < 0.05, NNT 8)
– no signi cant di erences in mortality, surgery requirement, or hospital stay
– Reference - Br J Surg 2011 May;98(5):640

Other pre-endoscopic medications

● histamine H2 antagonists (H2 blockers) not recommended for patients with acute ulcer bleeding 2 )

● prokinetic drugs

⚬ may allow for better visualization during endoscopy 5

⚬ administer erythromycin 250 mg IV over 30-120 minutes pre-endoscopy to improve diagnostic

yield and decrease need for repeat endoscopy (ACG Conditional recommendation; ESGE Strong
recommendation, High-quality evidence) 4 , 6

STUDY
⚬ SUMMARY
erythromycin before endoscopy may increase likelihood of completely empty stomach in
patients with acute upper gastrointestinal bleed DynaMed Level 2

SYSTEMATIC REVIEW: Aliment Pharmacol Ther 2011 Jul;34(2):166

Details
– based on systematic review limited by clinical heterogeneity
– systematic review of 4 randomized trials comparing preprocedural erythromycin to placebo or
no treatment in 335 patients with acute upper GI bleeding having urgent endoscopy
– treatment included nasogastric tube placement and gastric lavage prior to erythromycin
infusion in 2 trials, and no nasogastric tube/lavage in 2 trials
– clinical heterogeneity in trials with patients with varices ranging from 28% to 100% and varying
doses of erythromycin used
– erythromycin associated with

● increased incidence of empty stomach during endoscopy (primary outcome)

⚬ risk ratio (RR) 1.9 (95% CI 1.53-2.37)

⚬ NNT 2-5 with 37% empty stomach in control group
⚬ no statistically signi cant heterogeneity but magnitude of e ect greater in trials without
gastric lavage
● decreased

⚬ need for second endoscopy (RR 0.56, 95% CI 0.36-0.88)

⚬ need for blood transfusion (p = 0.02)
⚬ length of hospital stay (p = 0.0007)

– no signi cant di erences in procedure time (analysis limited by heterogeneity) or mortality

– Reference - Aliment Pharmacol Ther 2011 Jul;34(2):166

● splanchnic vasoconstrictors

⚬ generally used only if variceal bleed suspected (see also Acute Variceal Hemorrhage - Treatment)
 ⚬ somatostatin and octreotide not recommended in patients with acute nonvariceal upper

gastrointestinal bleeding (ESGE Strong recommendation, Low-quality evidence) 6

Medications for coagulopathy

● correct coagulopathy (for example, patients on anticoagulants) but correction should not delay
endoscopy (ICUGB Conditional recommendation, Very low-quality evidence; ESGE Strong
recommendation, Low-quality evidence) 2 , 6
⚬ in patients with hemodynamic instability, administer vitamin K supplemented with prothrombin
complex concentrate (PCC) or fresh frozen plasma if PCC unavailable (ESGE Strong
recommendation, Low-quality evidence)
⚬ consider international normalized ratio (INR) < 2.5 before endoscopy with or without hemostasis
(ESGE Weak recommendation, Moderate-quality evidence)
⚬ temporarily discontinue direct oral anticoagulants in patients with suspected acute nonvariceal
upper gastrointestinal bleeding in coordination with local hematologist/cardiologist (ESGE Strong
recommendation, Very low-quality evidence)

● do not use tranexamic acid in patients with upper nonvariceal gastrointestinal bleeding (ESGE Strong

recommendation, Low-quality evidence) 6

● use algorithm for patients on antiplatelet therapy with acute nonvariceal upper gastrointestinal

bleeding (ESGE Strong recommendation, Moderate-quality evidence) 6

⚬ for low risk stigmata identi ed with endoscopy

– if antiplatelet therapy for primary prophylaxis, withhold low-dose aspirin, re-evaluate risks and
bene ts of ongoing low-dose aspirin, and resume low-dose aspirin at hospital discharge if
clinically indicated
– if antiplatelet therapy for secondary prophylaxis (known cardiovascular disease)

● and patient only on low-dose aspirin, continue low-dose aspirin without interruption
● and patient on dual antiplatelet therapy, continue dual antiplatelet therapy without
interruption
⚬ for high risk stigmata identi ed with endoscopy

– if antiplatelet therapy for primary prophylaxis, withhold low-dose aspirin, re-evaluate risks and
bene ts of ongoing low-dose aspirin, and resume low-dose aspirin after ulcer healing or earlier
if clinically indicated
– if antiplatelet therapy for secondary prophylaxis

● and patient only on low-dose aspirin

⚬ resume low-dose aspirin by day 3 after index endoscopy

⚬ consider second-look endoscopy at discretion of endoscopist

● and patient on dual antiplatelet therapy

⚬ continue low-dose aspirin without interruption

⚬ consult cardiologist early for recommendation on resumption/continuation of second
antiplatelet agent
⚬ consider second-look endoscopy at discretion of endoscopist

⚬ for patients on non-aspirin antiplatelet monotherapy, administer low-dose aspirin as alternative if

no allergy or contraindication present

STUDY
● SUMMARY
tranexamic acid does not reduce death due to bleeding or 28-day all-cause mortality in adults
with acute gastrointestinal bleeding DynaMed Level 1

RANDOMIZED TRIAL: Lancet 2020 Jun 20;395(10241):1927 | Full Text

Details
⚬ based on randomized trial
⚬ 12,009 adults (mean age 58 years) with acute upper or lower gastrointestinal bleeding were
randomized to tranexamic acid vs. normal saline placebo and were followed for up to 28 days
– all patients were considered at risk of bleeding to death due to hypotension, tachycardia, or
signs of shock, or were likely to need transfusion, urgent endoscopy, or surgery
– variceal bleeding suspected in 45%

⚬ tranexamic acid dosing: 1 g in 100 mL 0.9% sodium chloride (normal saline) IV over 10 minutes
(loading dose) followed by 3 g in 1 L normal saline at 125 mg/hour for 24 hours (maintenance dose)
⚬ primary outcome was changed from 28-day all-cause mortality due to death from bleeding within 5
days (relative risk reduction of 25% was considered clinically important)
⚬ 99.4% included in analysis
⚬ comparing tranexamic acid vs. placebo

– death due to bleeding ≤ 5 days in 3.7% vs. 3.8% (risk ratio 0.99, 95% CI 0.82-1.18)
– 28-day all-cause mortality 9.5 vs. 9.2% (not signi cant)
– venous thromboembolic events in 0.8% vs. 0.4% (p < 0.05, NNH 250), signi cant, but may not be
clinically important
– seizure in 0.6% vs. 0.4% (p < 0.5, NNH 500), signi cant, but may not be clinically important
– myocardial infarction or stroke in 0.7% vs. 0.8% (not signi cant)

⚬ no signi cant di erence in death due to bleeding at 24 hours or 28 days or in rebleeding at 24

hours, 5 days, or 28 days
⚬ Reference - HALT-IT trial (Lancet 2020 Jun 20;395(10241):1927 full-text )

STUDY
● SUMMARY
tranexamic acid might reduce upper gastrointestinal bleeding DynaMed Level 2 , but not well
studied in patients receiving endoscopic treatment

COCHRANE REVIEW: Cochrane Database Syst Rev 2014 Nov 21;(11):CD006640

Details
⚬ based on Cochrane review limited by heterogeneity
⚬ systematic review of 8 randomized trials evaluating tranexamic acid for suspected or con rmed
upper gastrointestinal bleeding
⚬ analyses limited by heterogeneity in methods for detection and de nitions of bleeding
⚬ generalizability limited because most trials conducted before standard use of endoscopic
interventions
⚬ comparing tranexamic acid to placebo

– tranexamic acid associated with

● nonsigni cantly decreased risk of clinical or endoscopic bleeding (rebleeding or continued

bleeding) (risk ratio [RR] 0.72, 95% CI 0.5-1.03) in analysis of 7 trials with 1,651 patients,
results limited by signi cant heterogeneity
● nonsigni cantly decreased risk of surgery (RR 0.61, 95% CI 0.35-1.04) in analysis of 7 trials
with 1,551 patients, results limited by signi cant heterogeneity
 ● reduced mortality in analysis of 8 trials with 1,701 patients

⚬ RR 0.6 (95% CI 0.42-0.87)

⚬ NNT 21-96 with 8% mortality in placebo group

– no signi cant di erences in

● need for transfusion in analysis of 5 trials with 931 patients

● risk of any thromboembolic event in analysis of 4 trials with 1,095 patients

⚬ no signi cant di erences in bleeding, surgery, mortality, and need for transfusion comparing
tranexamic acid to cimetidine or lansoprazole in analyses of 2 trials with 720 patients
⚬ Reference - Cochrane Database Syst Rev 2014 Nov 21;(11):CD006640

Endoscopy

General information

● contraindications to EGD

⚬ absolute contraindications

– risks outweigh bene ts

– known or suspected peritonitis or gastrointestinal perforation
– respiratory distress, stridor, hypoxemia
– wound dehiscence

⚬ relative contraindications

– severe sepsis
– severe hypotension, shock
– obstructing pharyngeal or laryngeal lesion, severe hypopharyngeal trauma
– severe coagulopathy (INR > 3, platelet count < 30,000/mm3)

⚬ Reference - Med Clin North Am 2002 Nov;86(6):1165

● discharge from emergency department without inpatient endoscopy may be considered in stable
patients with following characteristics (representing Glasgow Blatchford score of 0), as evidence
suggests they have < 1% chance of requiring intervention (ACG Conditional recommendation) 4
⚬ urea nitrogen < 18.2 mg/dL
⚬ hemoglobin ≥ 13 g/dL for men (12 g/dL for women)
⚬ systolic blood pressure ≥ 110 mm Hg
⚬ pulse < 100 beats/minute
⚬ absence of melena, syncope, cardiac failure, and liver disease

● use stigmata of recent hemorrhage, based on Forrest criteria, as predictors of further risk of bleeding
and to guide management decisions (ACG Strong recommendation; ESGE Strong recommendation,
High-quality evidence) 4
⚬ stigmata of ulcer disease in descending risk of further bleeding (ACG Strong recommendation)

– active spurting
– nonbleeding visible vessel
– active oozing
– adherent clot
– at pigmented spot
– clean base
● guideline recommendations for endoscopic treatment of peptic ulcers 2 , 4 , 6

⚬ active spurting or oozing bleeding (Forrest classi cation IA and IB) or a nonbleeding visible vessel
(Forrest classi cation IIA) should be treated endoscopically (ACG Strong recommendation; ESGE
Strong recommendation, High-quality evidence)
⚬ for patients with an adherent clot (Forrest classi cation IIB) resistant to vigorous irrigation
endoscopic therapy should be considered, which may include endoscopic removal followed by
hemostasis (ACG Conditional recommendation; ICUGB Grade 2B ; ESGE Weak recommendation,
Moderate-quality evidence)
⚬ therapeutic bene t of clot treatment may be greater in patients with clinical features associated
with a higher risk of rebleeding (such as older age, concurrent illness, inpatient at time bleeding
began)
⚬ clean base (about 55% of patients)

– endoscopic therapy should not be given to patients who have an ulcer with a clean base
(Forrest classi cation III) or a at pigmented spot (Forrest classi cation IIC) (ACG Strong
recommendation; ESGE Weak recommendation, Moderate-quality evidence)
– patients with clean-based ulcers may receive a regular diet and be discharged after endoscopy
assuming (ACG Strong recommendation)
● hemodynamically stability
● stable hemoglobin level
● absence of other medical problems
● patient can be discharged to location where they can be observed by a responsible adult

IMAGE 2 OF 2

Clean-based ulcer

Clean-based gastric ulcer with no blood vessels,

pigmented spots, protuberances, or clots noted in
the base of this ulcer. This ulcer is at low risk for
rebleeding; endoscopic therapy is not indicated.

⚬ 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; clear
liquids may be taken soon after endoscopy (ACG Conditional recommendation)
⚬ do not routinely use Doppler ultrasound or magni cation endoscopy for evaluation of stigmata
(ESGE Strong recommendation, Low-quality evidence)

● consider endoscopic hemostasis for arteriovenous malformations, Mallory-Weiss tears, Dieulafoy's

lesions 3 , 6

● for variceal bleeding - see Acute Variceal Hemorrhage - Treatment

Timing

● timing of endoscopy

⚬ endoscopy should be done within 24 hours for most patients with acute upper gastrointestinal (GI)
bleeding (ICUGB Conditional recommendation, Very low-quality evidence; SIGN Grade C; ACG
 Conditional recommendation; ESGE Strong recommendation, Moderate-quality evidence) 1 , 2 , 4 , 6
⚬ in patients with higher risk clinical features (such as tachycardia, hypotension, bloody emesis, or
bloody nasogastric aspirate in hospital), endoscopy within 12 hours may be considered to
potentially improve clinical outcomes (ACG Conditional recommendation; ESGE Strong
recommendation, Moderate-quality evidence) 4 , 6
⚬ patients who are hemodynamically stable and without serious comorbidities should have
endoscopy as soon as possible in a nonemergent setting to identify those with low-risk endoscopic
ndings who can be safely discharged (ACG Conditional recommendation) 4

STUDY
⚬ SUMMARY
early endoscopy appears safe and may reduce duration of hospitalization compared to delayed
endoscopy in patients with nonvariceal upper gastrointestinal hemorrhage DynaMed Level 2

SYSTEMATIC REVIEW: Arch Intern Med 2001 Jun 11;161(11):1393

Details
– based on systematic review of trials with methodologic limitations
– systematic review of 23 studies (4 randomized trials, 19 nonrandomized and observational
studies) comparing early to delayed endoscopy in patients with nonvariceal upper
gastrointestinal tract hemorrhage presenting to emergency department (ED)
– all randomized trials had ≥ 1 methodologic limitation including

● lack of blinding of outcome assessor

● lack of allocation concealment
● lack of intention-to-treat analysis

– risk strati cation reported to be based on combination of clinical and endoscopic criteria
– in highest-quality randomized trial of low-risk patients, 110 patients were randomized to early
endoscopy (within 2 hours of presentation to ED) vs. delayed endoscopy (within 24-48 hours of
presentation to ED)
● 46% of early endoscopy group were immediately discharged
● no signi cant complications or readmissions reported in early endoscopy group at 1-month
follow-up
– in only randomized trial of high-risk patients, 124 patients were randomized to early endoscopy
(< 12 hours of presentation to ED) vs. delayed endoscopy (12-24 hours of presentation to ED)
● early endoscopy associated with decrease in transfusion requirements and length of stay in
subgroup of patients with bloody nasogastric aspirate
● no signi cant di erence in mortality between groups

– 7 of 8 studies evaluating resource utilization reported signi cant reduction in length of stay with
early endoscopy vs. delayed endoscopy
– Reference - Arch Intern Med 2001 Jun 11;161(11):1393

STUDY
⚬ SUMMARY
in adults with acute upper gastrointestinal bleeding at high risk for further bleeding or death,
endoscopy within 6 hours of consultation with gastroenterologist may not reduce 30-day all-
cause mortality compared to endoscopy between 6 and 24 hours DynaMed Level 2

RANDOMIZED TRIAL: N Engl J Med 2020 Apr 2;382(14):1299

Details
 – based on randomized trial with wide con dence interval
– 516 adults (mean age 70 years, 63% men) with overt signs of acute upper gastrointestinal
bleeding and at high risk for further bleeding or death (Glasgow-Blatchford score ≥ 12) were
randomized to urgent endoscopy within 6 hours vs. early endoscopy between 6 and 24 hours
and followed for 30 days
● all patients received proton pump inhibitor 80 mg IV bolus followed by 8 mg/hour
● patients with suspected variceal bleeding received vasoactive drug plus IV antibiotics

– patients with persistent hypotensive shock after resuscitation were excluded

– further bleeding de ned as composite of persistent bleeding or recurrence of bleeding after
hemostatic treatment
– 100% completed follow-up and included in analysis
– comparing urgent endoscopy group vs. early endoscopy group

● peptic ulcer in 61% vs. 61%

● esophagogastric varices in 9.7% vs. 7.3%
● mean time from presentation to endoscopy 9.9 hours vs. 24.7 hours

– comparing urgent endoscopy vs. early endoscopy

● 30-day all-cause mortality 8.9% vs. 6.6% (hazard ratio [HR] 1.35, 95% CI 0.72-2.54), not
signi cant, but CI includes possibility of bene t or harm
● further bleeding

⚬ within 7 days in 5.8% vs. 5.4% (HR 1.07, 95% CI 0.53-2.17)

⚬ within 30 days in 10.9% vs. 7.8% (HR 1.46, 95% CI 0.83-2.58)
⚬ endoscopic treatment given during rst endoscopy in 60.1% vs. 48.4% (p < 0.05)

– no signi cant di erences in intensive care unit admissions or red-cell transfusions

– Reference - N Engl J Med 2020 Apr 2;382(14):1299

Endoscopic therapy options and efficacy

● options for endoscopic therapy are categorized into 3 treatment modalities 5

⚬ injection

– diluted epinephrine (1:10,000 or 1:20,000) is commonly used and produces tamponade from
volume e ect and possibly vasoconstriction
– tissue adhesives including thrombin, brin, and cyanoacrylate glues may also be injected to seal
site of primary bleeding
⚬ thermal (contact or noncontact)

– contact devices include heater probes and bipolar electrocautery probes

– noncontact devices include argon plasma coagulation
– heat from thermal devices causes edema, tissue protein coagulation, vessel contraction, and
indirect activation of coagulation cascade leading to hemostatic bond
– contact devices also coagulate blood vessels by combining local tamponade (probe tip pressure
on bleeding site) with heat or electric current
⚬ mechanical

– clips (also called hemoclips) and band ligation devices achieving hemostasis through mechanical
compression
– used directly on bleeding site and slough o within days or weeks of placement
– clips are used most commonly, but band ligation may also be e ective (especially in patients
with Dieulafoy lesions)
● endoscopic therapies may be used individually or in combination to control bleeding 5

● guideline recommendations for endoscopic therapy for bleeding peptic ulcers 1 , 2 , 4 , 6

⚬ thermal therapy with bipolar electrocoagulation or heater probe and injection of sclerosant (such
as absolute alcohol) are recommended (ACG Strong recommendation; ICUGB Strong
recommendation, Low-quality evidence)
⚬ epinephrine therapy should not be sole therapy; combine with a second modality if used (ACG
Strong recommendation; SIGN Grade A; ESGE Strong recommendation, High-quality evidence)
⚬ endoscopic clips can be recommended (ACG Conditional recommendation; ICUGB Conditional
recommendation, Very low-quality evidence)
– clips appear to decrease further bleeding and need for surgery
– comparisons of clips vs. other therapies have variable results and currently used clips have not
been well studied
⚬ for 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 (ACG Conditional
recommendation; ESGE Strong recommendation, High-quality evidence)
⚬ for patients with active nonvariceal bleeding not controlled by standard hemostasis therapies,
consider topical hemostatic spray or over-the-scope clips as salvage therapy (ESGE Weak
recommendation, Low-quality evidence)
⚬ for patients with nonbleeding visible vessel, use mechanical therapy, thermal therapy, or injection
of sclerosant as monotherapy or in combination with epinephrine injection; do not use
epinephrine as monotherapy (ESGE Strong recommendation, High-quality evidence)
⚬ laser, monopolar electrocoagulation, argon plasma coagulation, and injection of thrombin or brin
glue considered second-line due to limited evidence of e cacy

● guideline recommendations for endoscopic therapy for upper nonvariceal gastrointestinal bleeding

not caused by peptic ulcers 6

⚬ for patients with acid-related causes di erent from peptic ulcers, treat with high-dose proton-
pump inhibitors (PPI); endoscopic treatment usually not required and select patients may be
discharged early (ESGE Strong recommendation, Low-quality evidence)
⚬ for patients with Mallory-Weiss lesion, use endoscopic hemostasis if actively bleeding or high-dose
PPI if no active bleeding present (ESGE Strong recommendation, Moderate-quality evidence)
⚬ for patients with Dieulafoy's lesion

– use endoscopic hemostasis with thermal, mechanical, or combination therapy (ESGE Strong
recommendation, Moderate-quality evidence)
– use transcatheter angiographic embolization or surgery if endoscopic treatment fails or is not
feasible (ESGE Strong recommendation, Low-quality evidence)
⚬ for patients bleeding from upper gastrointestinal angioectasias, use endoscopic hemostasis; no
speci c modality recommended (ESGE Strong recommendation, Low-quality evidence)
⚬ for patients bleeding from upper gastrointestinal neoplasia, consider endoscopic hemostasis to
avert urgent surgery and reduce blood transfusion requirements; no endoscopic modality appears
to have long-term e cacy (ESGE Weak recommendation, Low-quality evidence)

STUDY
● SUMMARY
among endoscopic therapy options, endoscopic clips with or without injection therapy
associated with better clinical outcomes than injection therapy alone, and thermal coagulation
combined with injection therapy associated with better clinical outcomes than either injection or
thermal coagulation therapy alone in patients with upper gastrointestinal bleeding due to peptic
ulcer DynaMed Level 2

SYSTEMATIC REVIEW: Surg Endosc 2016 Jun;30(6):2155

Details
⚬ based on systematic review with incomplete assessment of trial quality
⚬ systematic review of 28 trials evaluating endoscopic hemostatic modalities in 2,988 patients with
upper gastrointestinal bleeding due to peptic ulcer
⚬ trials compared endoscopic clips (hemoclips) vs. injection therapy (6 trials), hemoclips vs. hemoclip
plus injection (4 trials), hemoclips plus injection vs. injection alone (4 trials), hemoclips vs. thermal
coagulation (5 trials), thermal coagulation alone vs. injection alone (13 trials), thermal coagulation
vs. thermal coagulation plus injection (2 trials), and thermal coagulation plus injection vs. injection
alone (2 trials)
⚬ trial quality assessed using Jadad scale which does not include allocation concealment or intention-
to-treat analysis
⚬ comparing hemoclips to injection

– hemoclips associated with

● reduction in rebleeding rate in analysis of 5 trials with 456 patients

⚬ risk di erence (RD) 13% (95% CI 8%-19%)

⚬ NNT 6-13 with rebleeding in 20% of injection group

● reduction in emergency surgery rate in analysis of 5 trials with 456 patients

⚬ RD 5% (95% CI 1%-9%)
⚬ NNT 12-100 with emergency surgery in 9% of injection group

– no signi cant di erences in initial hemostasis or mortality in analysis of 5 trials with 456 patients

⚬ comparing hemoclips to hemoclips plus injection, no signi cant di erences in achieving initial
hemostasis, rebleeding rate, emergency surgery rate, or mortality in analysis of 3 trials with 237
patients
⚬ comparing hemoclips plus injection vs. injection alone

– hemoclips plus injection associated with

● reduction in rebleeding rate in analysis of 3 trials with 272 patients

⚬ RD 10% (95% CI 3%-18%)

⚬ NNT 6-34 with rebleeding in 17% of injection alone group

● reduction in emergency surgery rate in analysis of 3 trials with 272 patients, results limited by
signi cant heterogeneity
⚬ RD 7% (95% CI 2%-12%)
⚬ NNT 9-50 with emergency surgery in 8% of injection alone group

– no signi cant di erences in initial hemostasis or mortality in analysis of 3 trials with 272 patients

⚬ comparing hemoclips to thermal coagulation

– hemoclips associated with nonsigni cant reduction in initial hemostasis rate (RD 4%, 95% CI 0-
9%) in analysis of 5 trials with 554 patients, results limited by signi cant heterogeneity
– no signi cant di erences in rebleeding rate, emergency surgery rate, or mortality in analysis of
5 trials with 554 patients, results limited by signi cant heterogeneity for rebleeding rate
⚬ comparing thermal coagulation to injection

– thermal coagulation associated with

 ● reduction in initial hemostasis rate in analysis of 13 trials with 1,138 patients, results limited
by signi cant heterogeneity
⚬ RD 3% (95% CI 0-6%)
⚬ NNH 16 to in nity with initial hemostasis in 93% of injection alone group

● no signi cant di erences in rebleeding rate, emergency surgery, or mortality in analysis of 13

trials with 1,138 patients
⚬ comparing thermal coagulation plus injection to thermal coagulation alone

– thermal coagulation plus injection associated with

● reduction in rebleeding rate in analysis of 2 trials with 178 patients, results limited by
signi cant heterogeneity
⚬ RD 11% (95% CI 2%-21%)
⚬ NNT 5-50 with rebleeding in 19% of thermal coagulation alone group

● nonsigni cant increase in initial hemostasis rate (RD 7%, 95% CI 0-14%) in analysis of 2 trials
with 178 patients, results limited by signi cant heterogeneity
– no signi cant di erences in emergency surgery rate or mortality in analysis of 2 trials with 178
patients
⚬ comparing thermal coagulation plus injection to injection alone

– thermal coagulation plus injection associated with

● reduction in rebleeding rate in analysis of 2 trials with 334 patients, results limited by
signi cant heterogeneity
⚬ RD 8% (95% CI 2-14%)
⚬ NNT 8-50 with rebleeding in 14% of injection alone group

● reduction in emergency surgery rate in analysis of 2 trials with 334 patients

⚬ RD 6% (95% CI 0-12%)
⚬ NNT 9 to in nity with emergency surgery in 11% of injection alone group

– no signi cant di erence in initial hemostasis rate or mortality in analysis of 2 trials with 334
patients
⚬ Reference - Surg Endosc 2016 Jun;30(6):2155

STUDY
● SUMMARY
hemostasis with over-the-scope clips may reduce persistent bleeding compared to through-
the-scope clips in adults with peptic ulcer rebleeding DynaMed Level 2

RANDOMIZED TRIAL: Gastroenterology 2018 Sep;155(3):674

Details
⚬ based on randomized trial without blinding of outcome assessors
⚬ 67 adults (median age 78 years) with peptic ulcer rebleeding within 7 days after successful
hemostasis were randomized to 1 of 2 groups
– hemostasis with over-the-scope clips
– hemostasis with through-the-scope clips (standard treatment)

⚬ 18 patients (55%) in over-the-scope clips group and 33 patients (100%) in standard treatment group
received injection therapy
⚬ injection therapies included

– adrenaline solution in 18 patients in over-the-scope clips group and in 31 patients in standard

treatment group
 – brin glue in 2 patients in standard treatment group
⚬ co-primary outcomes included

– persistent bleeding de ned as active (oozing or squirting) bleeding despite endoscopic therapy
according to protocol
– recurrent bleeding de ned as any of active bleeding of endoscopically treated ulcer, adherent
clot at ulcer, or visible vessel with presence of fresh blood/clots in stomach or duodenum within
7 days after successful hemostasis
⚬ 10 patients with persistent bleeding after standard treatment crossed over to over-the-scope clips
group as permitted in protocol
⚬ 66 patients completed trial and were included in analyses
⚬ comparing over-the-scope clips vs. standard treatment

– further bleeding (composite of persistent or recurrent bleeding within 7 days) in 15.2% vs. 57.6%
(p = 0.001, NNT 3)
– persistent bleeding in 6.1% vs. 42.4% (p = 0.001, NNT 3)
– recurrent bleeding in 9.6% vs. 16.1% (not signi cant)
– in-hospital mortality 9.1% vs. 3% (not signi cant)
– 30-day overall mortality 12.1% vs. 6.3% (not signi cant)

⚬ Reference - STING trial (Gastroenterology 2018 Sep;155(3):674 )

STUDY
● SUMMARY
addition of second endoscopic method (sclerosing agent, mechanical hemostasis, or thermal
device) after epinephrine injection may reduce further bleeding and need for emergency surgery
in patients with major hemorrhage from peptic ulcers DynaMed Level 2

COCHRANE REVIEW: Cochrane Database Syst Rev 2014 Oct 13;(10):CD005584

Details
⚬ based on Cochrane review of trials without blinding
⚬ systematic review of 19 randomized trials comparing epinephrine injection plus second endoscopic
method vs. epinephrine injection alone in 2,033 adults with hemorrhage from peptic ulcer disease
and major stigmata of bleeding
⚬ second methods included sclerosants (ethanol, polidocanol, ethanolamine, or tetradecyl sulphate),
adhesive agents (cyanoacrylate), thrombotics ( brin glue or thrombin), thermal agents, and
mechanical methods (clips)
⚬ addition of second endoscopic method to epinephrine injection associated with

– reduced further bleeding (persistent or recurrent bleeding) in analysis of 19 trials with 1,926
patients, results limited by signi cant heterogeneity
● risk ratio (RR) 0.57 (95% CI 0.43-0.76)
● NNT 8-19 with further bleeding in 22% of epinephrine injection alone group
● no signi cant di erence found in subgroup of 10 trials with second-look endoscopies
(endoscopically con rmed rebleeding)
– reduced need for emergency surgery in analysis of 18 trials with 1,841 patients

● RR 0.68 (95% CI 0.5-0.93)

● NNT 18-130 with emergency surgery in 11% of epinephrine injection alone group

– nonsigni cant decrease in mortality (RR 0.64, 95% CI 0.39-1.06) in analysis of 18 trials with 1,841
patients
⚬ risk of further bleeding decreased for all types of second procedure in subgroup analyses
 ⚬ no signi cant di erence in adverse e ects in analysis of 12 trials with 1,281 patients, but few
events overall
⚬ Reference - Cochrane Database Syst Rev 2014 Oct 13;(10):CD005584

STUDY
● SUMMARY
endoscopic treatment with epinephrine injection plus thermocoagulation reduces rebleeding in
patients with bleeding peptic ulcers with nonbleeding visible vessels or adherent clots
DynaMed Level 1

RANDOMIZED TRIAL: Ann Intern Med 2003 Aug 19;139(4):237 | PDF

Details
⚬ based on randomized trial
⚬ 156 patients with history of upper gastrointestinal hemorrhage within previous 24 hours
randomized to endoscopic therapy vs. sham endoscopic therapy
– endoscopic therapy consisted of epinephrine 1:10,000 dilution injected to induce blanching and
edema (about 5 mL) then thermocoagulation with 30 joules for 6 seconds, mini-snare to remove
adherent clots
– sham endoscopic therapy consisted of gentle irrigation of ulcer base without manipulation

⚬ all patients had either nonbleeding visible vessels or adherent clots identi ed at endoscopy
⚬ all patients treated with omeprazole bolus infusion 80 mg during endoscopy followed by 8 mg/hour
for 72 hours
⚬ all patients given omeprazole 20 mg/day orally (outpatient maintenance) and 1-week triple therapy
if Helicobacter pylori infection
⚬ comparing endoscopic therapy vs. sham endoscopic therapy

– 0% vs. 9% had recurrent ulcer bleeding before discharge (p = 0.01, NNT 11)
– 1.1% vs. 11.6% had recurrent bleeding within 30 days (p = 0.009, NNT 9.5)
– 1 patient treated with endoscopic therapy had surgery for ulcer perforation (0 with sham
endoscopy)
– 2.6% vs. 5.1% died within 30 days (p > 0.2)

⚬ Reference - Ann Intern Med 2003 Aug 19;139(4):237 PDF , editorial can be found in Ann Intern
Med 2003 Aug 19;139(4):294 , commentary can be found in Ann Intern Med 2004 May
18;140(10):845

STUDY
● SUMMARY
endoscopic therapy with combination of heater probe plus injection associated with lower rate of
repeat endoscopy compared to injection alone in patients with peptic ulcer hemorrhage
DynaMed Level 2

COHORT STUDY: Dig Dis Sci 2010 Sep;55(9):2568

Details
⚬ based on cohort of 12,392 adults who had esophagogastroduodenoscopy for hematemesis,
melena, or suspected upper GI bleed
⚬ ≥ 1 peptic ulcer in 3,692 patients

– active bleeding in 10.7% (93% had endoscopic therapy)

– nonbleeding visible vessel in 6.3% (95% had endoscopic therapy)

⚬ repeat endoscopy within 72 hours of index endoscopy in 1,646 patients

 ⚬ repeat endoscopy rates

– 12.2% for injection monotherapy

– 6.1% for heater probe monotherapy (not signi cant vs. injection monotherapy)
– 7.1% for combination heater probe plus injection (p = 0.02 vs. injection monotherapy)

⚬ immediate hemostasis rates 88%-97% across all types of therapies

⚬ no signi cant di erences in hemostasis rates among therapy types
⚬ Reference - Dig Dis Sci 2010 Sep;55(9):2568

● TC-325 is mineral-based powder sprayed endoscopically onto bleeding site

STUDY
⚬ SUMMARY
TC-325 hemostatic powder reported to have high rate of immediate hemostasis in adults with
upper gastrointestinal bleeding, with rebleeding in about one-third at 30 days
DynaMed Level 3

CASE SERIES: Endoscopy 2016 Dec;48(12):1084

Details
– based on case series
– 202 adults (mean age 68 years) with upper gastrointestinal bleeding treated with TC-325
hemostatic powder alone or in combination with other treatments were assessed
– etiology of bleeding

● ulcer in 37%
● malignant lesion in 30%
● postendoscopic bleeding in 17%
● other causes in 15%

– 46.5% had TC-325 as rst-line treatment and 53.5% had TC-325 as salvage therapy
– immediate hemostasis in 96.5%; consistent results for rst-line vs. salvage therapy
– recurrence of upper gastrointestinal bleeding in 26.7% at 8 days and in 33.5% at 30 days
– risk factors for bleeding recurrence in multivariable analysis

● melena at initial presentation associated with increased risk at 8 and 30 days

● TC-325 as salvage therapy associated with increased risk at 8 days

● pulsatile bleeding at initial endoscopy associated with increased risk at 30 days

– no severe adverse events reported

– Reference - GRAPHE Registry study (Endoscopy 2016 Dec;48(12):1084 , editorial [in French]
can be found in Endoscopy 2016 Dec;48(12):1150 )

● cyanoacrylate spray during endoscopy reported to be e ective for persistent upper gastrointestinal
bleeding in case series of 5 patients, 2 of whom developed rebleeding (Gastrointest Endosc 2013
Sep;78(3):536 )

STUDY
● SUMMARY
argon plasma coagulation therapy not proven superior to other endoscopic therapies for acute
nonvariceal upper gastrointestinal bleeding

COCHRANE REVIEW: Cochrane Database Syst Rev 2009 Oct 7;(4):CD003791

Details
 ⚬ based on withdrawn Cochrane review
⚬ Reference - systematic review of 2 randomized trials with 121 patients last updated 2005 Feb 4
(Cochrane Database Syst Rev 2009 Oct 7;(4):CD003791 )

⚬
DynaMed Commentary

Cochrane review was withdrawn 2009 Aug 5 because Cochrane has lost contact with the
authors.

Repeat endoscopy

● repeat endoscopy should not be routinely performed, but may be necessary in patients with signs of

recurrent bleeding or uncertainty about e ectiveness of hemostasis 5

● recommendations for repeat and second-look endoscopy

⚬ repeat endoscopy in patients with clinical evidence of recurrent bleeding, using hemostatic therapy
for patients with higher risk stigmata of hemorrhage (ACG Strong recommendation; ESGE Strong
recommendation, High-quality evidence) 4 , 6
⚬ if bleeding occurs after treatment with second endoscopy, consider surgery or interventional
radiology with transcatheter arterial embolization (ACG Conditional recommendation; ESGE Strong
recommendation, High-quality evidence) 4 , 6
⚬ routine second-look endoscopy, in which repeat endoscopy is performed 24 hours after initial
endoscopic hemostatic therapy, is not recommended (ACG Conditional recommendation; ICUGB
Grade 2B), but may be considered if patient is at high risk of rebleeding (ESGE Strong
recommendation, High-quality evidence) 2 , 4 , 6
⚬ Scottish Intercollegiate Guidelines Network (SIGN) recommendations 1

– repeat endoscopy and endotherapy within 24 hours if (SIGN Grade B)

● initial endoscopic treatment considered suboptimal due to di cult access, poor visualization
or technical di culties
● rebleeding likely to be life-threatening

– follow-up endoscopy should con rm healing of gastric ulcers if suspicion of malignancy (SIGN
Good Practice Point)

STUDY
● SUMMARY
routine second-look endoscopy after endoscopic hemostasis of peptic ulcer bleeding possibly
associated with reduced rebleeding and surgery in patients with very high risk of bleeding
DynaMed Level 2

SYSTEMATIC REVIEW: Gastrointest Endosc 2012 Aug;76(2):283

Details
⚬ based on systematic review limited by clinical heterogeneity
⚬ systematic review of 8 randomized trials comparing routine second-look endoscopy to close
observation for signs of rebleeding after initial endoscopy for gastric or duodenal ulcer bleeding in
938 patients
⚬ all patients had
 – initial endoscopy within 4-24 hours of admission, high-risk stigmata, and successful hemostasis
– follow-up for 30 days or until discharge

⚬ second-look endoscopy within 16-48 hours of initial endoscopy

⚬ clinical heterogeneity among trials included di erences in endoscopic therapy, use of proton pump
inhibitors (PPIs), de nitions of rebleeding, and patient risk level
⚬ second-look endoscopy associated with reduced

– rebleeding (odds ratio [OR] 0.55, 95% CI 0.37-0.81) in analysis of 8 trials with 938 patients,
results not signi cant after removal of 2 trials
● greater bene t reported in 2 trials with 234 very high-risk patients (high prevalence of active
bleeding or shock)
● no signi cant di erence in 1 trial of high-dose PPI

– surgery (OR 0.43, 95% CI 0.19-0.96) in analysis of 5 trials with 607 patients

⚬ no signi cant di erences in mortality in analysis of 5 trials or units of blood transfused in analysis
of 2 trials
⚬ Reference - Gastrointest Endosc 2012 Aug;76(2):283

⚬ repeat endoscopy 16-24 hours after endoscopic hemostasis of bleeding peptic ulcer may
reduce recurrent bleeding and surgery rates
DynaMed Level 2

– based on randomized trial without blinding of outcome assessors

– 194 patients aged 15-90 years with endoscopically con rmed bleeding peptic ulcer and acute
bleeding, visible vessel, or adherent clot who had successful endoscopic hemostasis within 24
hours were randomized to scheduled second endoscopy 16-24 hours after initial endoscopy vs.
close observation
– 50% of patients had shock
– all patients treated with omeprazole 40 mg IV every 12 hours for 3 days after initial endoscopy
– comparing second endoscopy vs. close observation

● recurrent bleeding within 7 days in 4% vs. 14% (p = 0.027, NNT 11)

● recurrent bleeding within 30 days in 5% vs. 14% (p = 0.0314, NNT 12)
● surgery to stop recurrent bleeding in 1% vs. 6% (p = 0.05, NNT 19)
● no signi cant di erence in duration of hospital stay, transfusion, or mortality

– Reference - Gut 2003 Oct;52(10):1403 full-text

Doppler-guided endoscopic hemostasis

STUDY
● SUMMARY
Doppler guidance during endoscopic hemostasis reduces rebleeding in patients with severe
nonvariceal upper gastrointestinal bleeding DynaMed Level 1

RANDOMIZED TRIAL: Gastroenterology 2017 May;152(6):1310-1318.e1 | Full Text

Details
⚬ based on single-blind randomized trial
⚬ 148 patients (mean age 66 years, 80% male) with severe nonvariceal upper gastrointestinal (GI)
bleeding were randomized to endoscopic hemostasis assisted by Doppler monitoring of blood ow
(Doppler-guided hemostasis) vs. standard endoscopic hemostasis and followed for 30 days
⚬ patients had ulcers (84.4%), Dieulafoy lesions (12.8%), or Mallory Weiss tears (2.7%)
⚬ endoscopic treatment was
 – for Doppler-guided hemostasis - detection of arterial blood ow underneath stigmata of recent
hemorrhage prior to epinephrine injection or visually guided hemostasis and after hemostasis
● if active arterial bleeding, nonbleeding visible vessel, or adherent clot - epinephrine injection
plus thermal coagulation
● if additional bleeding or persistence of arterial signal in Doppler - hemoclips used resulting in
triple therapy
● if acute, small, or less brotic ulcers with nonbleeding visible vessel, adherent clots, or
Dieulafoy lesions or Mallory Weiss tears - epinephrine injection plus hemoclips
● if negative Doppler signal - no endoscopic therapy

– for standard treatment - epinephrine injection plus hemoclipping or epinephrine injection plus
thermal coagulation, or no endoscopic therapy if at spots
⚬ signi cantly more patients in Doppler-guided hemostasis group were using aspirin at baseline
(54.2% vs. 36.8%, p = 0.034)
⚬ comparing Doppler-guided hemostasis vs. standard hemostasis

– 30-day rebleeding in 11.1% vs. 26.3% (p = 0.0214, NNT 7)

– surgery required for rebleeding in 0% vs. 5.3% (p = 0.048, NNT 19)
– major complications in 0% vs. 5.3% (p = 0.048, NNT 19)

⚬ no signi cant di erence in mortality, length of stay in hospital or intensive care unit, transfusion, or
median time to rebleeding
⚬ Reference - Gastroenterology 2017 May;152(6):1310-1318.e1 full-text , commentary can be
found in Gastroenterology 2017 May;152(6):1280

Surgery and procedures

Surgery for bleeding peptic ulcers

● surgery not routinely needed for bleeding peptic ulcers but may have role if

⚬ hemodynamic stabilization cannot be achieved through volume repletion with crystalloid uids or
blood products
⚬ patient unlikely to tolerate recurrent or worsened bleeding
⚬ high risk of failure for repeat endoscopic hemostasis including

– ulcers > 2 cm in diameter

– hypotension associated with rebleeding episode

⚬ Reference - N Engl J Med 2008 Aug 28;359(9):928

● surgical resection for bleeding peptic ulcers

STUDY
⚬ SUMMARY
gastric resection with ulcer excision may lower rate of postoperative bleeding recurrence
compared to oversewing plus vagotomy for emergent surgical treatment of bleeding duodenal
ulcer DynaMed Level 2

RANDOMIZED TRIAL: World J Surg 1993 Sep-Oct;17(5):568

Details
– based on randomized trial without blinding of outcome assessors
– 120 patients having emergency surgery for massive, persistent, or recurrent bleeding from
duodenal ulcer randomized to gastric resection with ulcer excision vs. oversewing plus
vagotomy
 – 2 patients excluded after randomization
– postoperative bleeding recurrence de ned as rebleeding (diagnosed by broscopic
investigation, reoperation, or both, and requiring ≥ 1 unit of blood) occurring during same
hospital admission or during rst month after discharge
– comparing gastric resection vs. oversewing plus vagotomy

● postoperative bleeding recurrence in 3% vs. 17% (p < 0.05, NNT 8)

● duodenal leak in 13% vs. 3% (p < 0.1) but no di erence in intention-to-treat analysis including
leak after reoperations for rebleeding (12% vs. 13%)
● postoperative mortality 23% vs. 22% (not signi cant)

– Reference - World J Surg 1993 Sep-Oct;17(5):568

STUDY
⚬ SUMMARY
vagotomy plus resection appears no more effective than vagotomy plus drainage for
treatment of bleeding peptic ulcers DynaMed Level 2

MODELING STUDY: J Am Coll Surg 2006 Jan;202(1):78

Details
– based on prediction modeling from retrospective cohort study (Department of Veterans A airs
National Surgical Quality Improvement Program Database)
– 907 patients treated with vagotomy plus drainage or vagotomy plus resection for treatment of
bleeding peptic ulcer disease from 1991 to 2001
– no signi cant di erences comparing surgical approaches in 30-day mortality, morbidity, or rate
of rebleeding
– resection associated with prolonged hospital stay
– Reference - J Am Coll Surg 2006 Jan;202(1):78

Surgery and procedures for failed endoscopic therapy

Options

● seek surgical consultation for failed endoscopic therapy 2

● hemorrhage not controlled by endoscopy may be treated with one of following

⚬ repeat endoscopic therapy (SIGN Grade D) 1

⚬ selective angiographic embolization (also called transcatheter arterial embolization) (SIGN Grade D

; ICUGB Grade 2C) 1 , 2 )

⚬ surgery (SIGN Grade D) 1

● angiographic embolization may be especially useful in patients with high operative risk 5

Angiographic embolization

STUDY
● SUMMARY
prophylactic angiographic embolization after endoscopic hemostasis may reduce need for blood
transfusion but may not reduce recurrent bleeding within 30 days in patients with bleeding
peptic ulcers and ≥ 1 risk factor for recurrent bleeding

RANDOMIZED TRIAL: Gut 2019 May;68(5):796

 Details
⚬ based on randomized trial with wide con dence intervals
⚬ 241 patients (mean age 66 years, 75% men) with bleeding peptic ulcers and ≥ 1 risk factor for
recurrent bleeding were randomized after endoscopic hemostasis to angiographic embolization vs.
no embolization and followed for 30 days
⚬ risk factors for recurrent bleeding included ulcers ≥ 20 mm, spurting bleeding, hypotensive shock,
and hemoglobin < 9 g/dL
⚬ endoscopic treatment was hemoclipping or thermocoagulation with or without preinjection with
diluted epinephrine
⚬ both groups received

– bolus proton pump inhibitor 80 mg IV then 8 mg/hour for 3 days

– Helicobacter pylori eradication therapy starting on day 4

⚬ 18.6% randomized to angiographic embolization did not receive embolization

⚬ primary outcome was recurrent bleeding within 30 days
⚬ comparing angiographic embolization vs. no embolization

– rate of recurrent bleeding within 30 days in intention-to-treat and per protocol analyses (results
not signi cant, but con dence intervals for both analyses include possibility of both bene t and
harm)
● 10.2% vs. 11.4% (risk ratio [RR] 0.89, 95% CI 0.43-1.85) in intention-to-treat analysis (6 of 12
patients who re-bled in the embolization group had not received embolization)
● 6.2% vs. 11.4% (RR 0.55, 95% CI 0.22-1.38) in per-protocol analysis (excludes patients in
embolization group who did not have embolization)
– blood transfusion in 46.6% vs. 59.3% (RR 0.79, 95% CI 0.62-1), signi cant, but con dence interval
includes di erences that may not be clinically important
– treatment for recurrent bleeding in 11% vs. 13.8% (not signi cant)
– death within 30 days in 2.5% vs. 4.1% (not signi cant)

⚬ in post hoc analysis of 96 patients with ulcers ≥ 15 mm, 4.5% in embolization group had recurrent
bleeding vs. 23.1% in no embolization group (p = 0.027, NNT 6)
⚬ Reference - Gut 2019 May;68(5):796 , commentary can be found in Gut 2019 Aug;68(8):1529

⚬
DynaMed Commentary

Point estimates and 95% con dence intervals for recurrent bleeding and transfusion rate were
calculated by DynaMed editors.

STUDY
● SUMMARY
transcatheter arterial embolization with N-butyl cyanoacrylate reported to be clinically
successful in about 80% with major complications in about 2% of patients with upper
gastrointestinal bleeding DynaMed Level 3

SYSTEMATIC REVIEW: J Vasc Interv Radiol 2017 Apr;28(4):522

Details
⚬ based on systematic review of case series
 ⚬ systematic review of 15 retrospective case series reporting outcomes of transcatheter arterial
embolization with N-butyl cyanoacrylate (NBCA) in 440 patients (mean age 64 years, 73% male) with
gastrointestinal (GI) bleeding
– upper GI bleeding in 59.3% and lower GI bleeding in 40.7%
– 75.1% of patients with upper GI bleeding had failed endoscopic treatment

⚬ NBCA agent used was Histoacryl in 98.1% and Tru ll in 1.9%

⚬ technical success reported in 99.2% of patients with upper GI bleeding
⚬ pooled outcomes in 259 patients with upper GI bleeding and technical success of NBCA treatment

– clinical success (de ned as no recurrent bleeding within 30 days) in 81.1%

– major complications in 1.9%
– 30-day mortality 20.8%
– bleeding-related 30-day mortality 8.1%

⚬ Reference - J Vasc Interv Radiol 2017 Apr;28(4):522 , commentary can be found in J Vasc Interv
Radiol 2017 Jun;28(6):923

STUDY
● SUMMARY
transcatheter arterial embolization with N-butyl cyanoacrylate (NBCA) reported to stop ulcer
bleeding after failed endoscopic treatment DynaMed Level 3

CASE SERIES: Acta Radiol 2013 Oct;54(8):934

CASE SERIES: J Vasc Interv Radiol 2013 Mar;24(3):432

Details
⚬ based on 2 case series
⚬ 31 patients (mean age 66 years) with acute bleeding from gastroduodenal ulcers after failed
endoscopic treatment had transcatheter arterial embolization with NBCA
– 4 patients died of cardiovascular collapse and 6 discharged without follow-up endoscopy
– 21 patients had NBCA injection (via left gastric artery in 12, right gastric artery in 2, both left and
right gastric arteries in 2, duodenal branches in 4, and the gastroduodenal artery in 11)
– hemostasis demonstrated on postembolization arteriography in all patients and no recurrent
bleeding
– repeat endoscopy showed no ischemic mucosal changes
– Reference - Acta Radiol 2013 Oct;54(8):934

⚬ 15 patients (mean age 71.3 years) with nonvariceal gastroduodenal bleeding had transcatheter
arterial embolization with NBCA after failed endoscopic treatment
– embolization reported successful in 100%
– no recurrent bleeding or embolization
– Reference - J Vasc Interv Radiol 2013 Mar;24(3):432

STUDY
● SUMMARY
angiographic embolization for gastroduodenal hemorrhage reported to result in frequent
rebleeding DynaMed Level 3

CASE SERIES: Arch Surg 2008 May;143(5):457

Details
⚬ based on retrospective case series
 ⚬ 57 patients with gastroduodenal hemorrhage had angiographic embolization after failure of
endoscopic treatment
⚬ 49% had in-hospital rebleeding
⚬ 44% had in-hospital rebleeding after repeat embolization
⚬ poor outcomes associated with

– recent duodenal ulcer suture ligation

– blood transfusion > 6 units before embolization

⚬ Reference - Arch Surg 2008 May;143(5):457

Comparison between surgery and transcatheter arterial embolization

STUDY
● SUMMARY
transcatheter arterial embolization associated with increased risk of rebleeding compared to
surgery after failed endoscopic hemostasis in patients with upper nonvariceal gastrointestinal
bleeding DynaMed Level 2

SYSTEMATIC REVIEW: Endosc Int Open 2014 Mar;2(1):E6 | Full Text

Details
⚬ based on systematic review of cohort studies
⚬ systematic review of 6 retrospective cohort studies evaluating transcatheter arterial embolization
(TAE) and surgery in 423 patients with upper nonvariceal gastrointestinal bleeding who failed
endoscopic hemostasis
– embolization agents included coils, particles (gelatin sponge [Gelfoam] or polyvinyl alcohol), or
combination of coils and particles
– surgical procedures included duodenectomy with oversewing, gastrectomy plus reconstruction,
Billroth I procedure, Billroth II procedure, vagotomy plus drainage, and resection after Billroth
procedure
⚬ comparing TAE to surgery

– TAE associated with increased risk of rebleeding (RR 1.82 95% CI 1.23-2.67) in analysis of 6
studies with 419 patients
– no signi cant di erences in

● mortality in analysis of 6 studies with 423 patients

● need for additional intervention in analysis of 6 studies with 377 patients, results limited by
signi cant heterogeneity
– pooled complication rates

● in TAE 4% in in 5 studies with 158 patients

● in surgery 46% in 5 studies with 202 patients

⚬ consistent results in sensitivity analyses

⚬ Reference - Endosc Int Open 2014 Mar;2(1):E6 full-text

Additional management of bleeding peptic ulcers

General information

● all patients with bleeding peptic ulcer should be tested for Helicobacter pylori (ESGE Strong

recommendation, High-quality evidence) 6

● aspirin management

⚬ discontinue aspirin and nonsteroidal anti-in ammatory drugs (NSAIDs) if peptic ulcer bleeding;
only restart at low dose after ulcer healing and H. pylori eradication if clear indication (SIGN Grade
A; ESGE Strong recommendation, Low-quality evidence) 1 , 6
⚬ resume aspirin immediately after index endoscopy if risk of rebleeding is low; in patients with high-
risk peptic ulcer, restart aspirin within 3 days after index endoscopy if adequate hemostasis
achieved (ESGE Strong recommendation, Moderate-quality evidence) 6
⚬ in patients receiving dual antiplatelet therapy who develop peptic ulcer bleeding, continue low-
dose aspirin; consult with cardiologist on timing for restart of second antiplatelet agent (ESGE
Strong recommendation, Low-quality evidence) 6

● in patients with indication for long-term anticoagulation, restart anticoagulant therapy following

nonvariceal bleeding (ESGE Strong recommendation, Moderate-quality evidence) 6

⚬ timing should be assessed on individual patient basis
⚬ warfarin resumption between 7 and 15 days after bleeding appears safe and e ective in
preventing thromboembolic complications
⚬ resumption before day 7 after bleeding may be indicated for patients at high risk of thrombosis

● administer proton-pump inhibitor (PPI) therapy as co-therapy in patients who had upper nonvariceal
gastrointestinal bleeding and require dual antiplatelet therapy (ESGE Strong recommendation,
Moderate-quality evidence) 6

Helicobacter pylori testing

● guideline recommendations for peptic ulcer disease 1 , 2 , 4 , 6

⚬ test for H. pylori infection with biopsy, if bleeding peptic ulcer (ESGE Strong recommendation, Low-
quality evidence; ICUGB Grade 1A)
⚬ biopsy samples for H. pylori testing should be taken at initial endoscopy before starting proton
pump inhibitor; biopsy samples should be assessed histologically if rapid urease test negative
(SIGN Grade B)
⚬ give H. pylori eradication therapy if positive (ACG Strong recommendation; ICUGB Grade 1A ; SIGN
Grade A); see also Helicobacter pylori Infection
⚬ negative H. pylori tests in acute setting should be repeated (ICUGB Grade 1B ; ESGE Strong
recommendation, High-quality evidence)
⚬ successful H. pylori eradication should be con rmed by breath test, biopsy, or stool antigen test ≥ 1
month after treatment
⚬ give second-line treatment if eradication failure (SIGN Good Practice Point)
⚬ maintenance antisecretory therapy is not needed after H. pylori eradication unless patient also
requires NSAIDs or antithrombotics (ACG Strong recommendation; SIGN Grade A)

● as patients with documented peptic ulcer disease may have higher pretest probability of infection, IgG
H. pylori antibody testing may be useful (Am J Gastroenterol 2017 Feb;112(2):212 , correction can be
found in Am J Gastroenterol 2018 Jul;113(7):1102 )

STUDY
● SUMMARY
C-13 urea breath test may be most accurate test for H. pylori infection in patients with upper
gastrointestinal bleeding DynaMed Level 2
 SYSTEMATIC REVIEW: Am J Gastroenterol 2006 Apr;101(4):848

Details
⚬ based on systematic review with heterogeneity
⚬ systematic review assessed 6 di erent diagnostic tests for H. pylori infection in patients with upper
gastrointestinal bleeding

Table 6. Diagnostic Accuracy for H. Pylori Infection

Test Pooled Pooled Positive Negative Number

Sensitivi Speci cit Likelihoo Likelihoo of
ty y d Ratio d Ratio Studies
(Number
of
Patients)

Urea 93% 92% 9.5 0.11 8 (520)

breath
test

Stool 87% 70% 2.3 0.2 6 (377)

antigen
test

Serology 88% 69% 2.5 0.25 9 (803)

Rapid 67% 93% 9.6 0.31 16 (1,417)

urease
test
(biopsy)

Histology 70% 90% 6.7 0.93 10 (827)

(biopsy)

Culture 45% 98% 19.6 0.31 3 (314)

(biopsy)

Abbreviation: H. pylori, Helicobacter pylori.

⚬ Reference - Am J Gastroenterol 2006 Apr;101(4):848

Discharge planning

Timing of discharge
● International Consensus Upper Gastrointestinal Bleeding Conference Group recommendations 2 )

⚬ most patients who had endoscopic hemostasis for high-risk stigmata should be hospitalized for ≥
72 hours (ICUGB Grade 1C )
⚬ low-risk patients can be fed within 24 hours of endoscopy
⚬ selected low-risk patients with acute ulcer bleeding may be discharged after endoscopy (ICUGB
Grade 1A )
– early discharge plus outpatient care had similar risk of recurrent bleeding as inpatient care but
reduced cost in patients at low-risk for recurrent bleeding in 1 randomized trial summarized
below
– early discharge of low-risk patients after endoscopy also supported in observational studies as
complication rates (such as rebleeding, surgery, and mortality), health status, and satisfaction
were similar to those of inpatients

STUDY
● SUMMARY
early discharge (after endoscopy) plus outpatient care does not increase risk of recurrent
bleeding compared to inpatient care in patients with nonvariceal upper gastrointestinal
hemorrhage at low risk of recurrent bleeding DynaMed Level 1

RANDOMIZED TRIAL: Gastrointest Endosc 2002 Jan;55(1):1

Details
⚬ based on randomized trial
⚬ 95 patients with nonvariceal upper gastrointestinal hemorrhage at low risk of recurrent bleeding
were randomized to 1 of 2 groups
– early discharge (after endoscopy) plus outpatient care including examination by primary care
physician in rst week after discharge plus follow-up phone calls or visits on days 7, 14, 21, and
30
– inpatient care with decision for hospital discharge based on criteria such as absence of signs
and symptoms of recurrent bleeding, and stable hemoglobin level and vital signs
⚬ inclusion criteria (criteria for early discharge plus outpatient care)

– absence of

● varices and signs of portal hypertension

● high-risk stigmata of recent hemorrhage (active bleeding, visible vessel, or adherent clot) on
endoscopy
● hypovolemic shock
● orthostatic change in vital signs
● need for blood transfusion
● serious concurrent medical illness (Rockall score ≤ 4)

– hemoglobin > 8 g/dL, normal coagulation studies, easy accessibility to hospital, and adequate
sociofamily support
⚬ all patients had endoscopy within 12 hours of hemorrhage onset
⚬ comparing early discharge plus outpatient care vs. inpatient care

– median hospital stay 1 day vs. 4 days (p = 0.001)

– recurrent bleeding in 2.1% vs. 2.2% (not signi cant)
– median cost $340 vs. $3,940 (p = 0.001)

⚬ no patient had surgery or died

⚬ Reference - Gastrointest Endosc 2002 Jan;55(1):1
STUDY
● SUMMARY
selected patients treated by endoscopy for bleeding duodenal ulcers may be safely discharged
home after successful completion of the procedure DynaMed Level 2

COHORT STUDY: Gastrointest Endosc 1997 Jan;45(1):26

Details
⚬ based on cohort study with sample size too small to exclude uncommon adverse outcomes
⚬ retrospective study of 72 patients meeting criteria discharged on same day as endoscopy had no
episodes of rebleeding at 2 weeks
⚬ criteria

– age < 60 years old

– hemoglobin > 10 g/dL
– stable vital signs
– no stigmata on endoscopy except at spots (clean-based ulcer)
– no stigmata of recent hemorrhage and no coexisting medical illness

⚬ among 75 patients prospectively studied, no rebleeding at 1 week

⚬ Reference - Gastrointest Endosc 1997 Jan;45(1):26

STUDY
● SUMMARY
carefully selected elderly patients may be safely managed without hospital admission if
immediate upper endoscopy available DynaMed Level 2

COHORT STUDY: Am J Gastroenterol 1999 May;94(5):1242

Details
⚬ based on small cohort study
⚬ 84 elderly patients with upper gastrointestinal bleeding presenting mainly with hematemesis or
melena who were not orthostatic had immediate upper endoscopy
⚬ outpatient treatment provided for 24 patients with low-risk endoscopic ndings (such as white base
ulcer < 1.5 cm or erosive mucosal disease) and no other reason for admission
⚬ no patients treated as outpatients had rebleeding during prospective 1-month follow-up
⚬ Reference - Am J Gastroenterol 1999 May;94(5):1242

STUDY
● SUMMARY
timing of discharge after resolution of bleeding from peptic ulcer may be determined by findings
at endoscopy DynaMed Level 2

COHORT STUDY: Gastrointest Endosc 1996 Oct;44(4):382

Details
⚬ based on prospective cohort study
⚬ 392 patients with bleeding peptic ulcer and no coexistent acute illnesses had endoscopy within 24
hours of presentation with hematemesis or melena
⚬ on endoscopy active bleeding treated with epinephrine injection and thermocoagulation
⚬ number of days by ulcer type for risk of rebleeding to be < 3% within subsequent 10 days

– clean base - 0 days

– red or black spots - 3 days
 – adherent clots - 3 days
– nonbleeding visible vessels (no treatment) - 4 days
– nonbleeding visible vessels (treated) - 4 days
– bleeding visible vessels (treated) - 3 days

⚬ author recommendations

– patients with clean-base ulcers can be safely discharged on day of diagnosis

– patients with red or black spots, adherent clots, or bleeding visible vessels can be discharged on
day 3
– patients with nonbleeding visible vessels safe to discharge on day 4

⚬ Reference - Gastrointest Endosc 1996 Oct;44(4):382

Medication considerations at discharge

● discharge with prescription for single daily dose oral proton pump inhibitor (PPI) (duration based on

underlying etiology) (ICUGB Grade 1C ) 2 )

● in patients with severe esophagitis (Los Angeles esophagitis classi cation Grade C or D, or stricture),
consider twice-daily standard PPI dosing to relieve symptoms, reduce acid exposure, and promote
healing (CAG Level 1B) (Can J Gastroenterol 2005 Jan;19(1):15 )

● in patients with nonsteroidal anti-in ammatory drugs (NSAID)-associated bleeding ulcers 2 , 4

⚬ assess need for NSAIDs

⚬ if NSAIDs must be resumed, consider COX-2 selective NSAID at the lowest e ective dose plus daily
PPI (ACG Strong recommendation; ICUGB Grade 1B )

● in patients with low-dose aspirin-associated bleeding ulcers (ACG Conditional recommendation;

ICUGB Grade 1B ; ESGE Strong recommendation, Moderate-quality evidence) 2 , 4 , 6

⚬ assess need for aspirin
⚬ if needed for secondary prevention (for example, cardiovascular disease), restart aspirin as soon as
possible after bleeding stops, within 1-3 days, if possible and certainly within 7 days
⚬ use long-term daily PPI therapy
⚬ clopidogrel alone has higher risk for rebleeding than aspirin plus PPI

● in patients with idiopathic (non-Helicobacter pylori, non-NSAID) ulcers, long-term anti-ulcer therapy
such as daily PPI therapy is recommended (ACG Conditional recommendation)

● use caution with oral anticoagulants, corticosteroids, or selective serotonin reuptake inhibitors (SSRIs)

because of possible increased risk of gastrointestinal bleeding (SIGN Grade D) 1

STUDY
● SUMMARY
resumption of warfarin therapy associated with decreased risk of mortality and thrombosis
without significant increased risk of recurrent hemorrhage in patients with gastrointestinal
bleeding DynaMed Level 2

COHORT STUDY: Arch Intern Med 2012 Oct 22;172(19):1484

Details
⚬ based on retrospective cohort study
 ⚬ 442 patients (mean age 74 years) with gastrointestinal tract bleeding during warfarin therapy
evaluated for resumption of warfarin therapy and followed for 90 days
⚬ 58.8% resumed warfarin therapy
⚬ comparing resumption vs. no resumption of warfarin therapy

– thrombosis in 0.4% vs. 5.5% (p < 0.001)

– mortality in 5.8% vs. 20.3% (p < 0.001)
– recurrent gastrointestinal bleeding in 10% vs. 5.5% (p = 0.09)

⚬ Reference - Arch Intern Med 2012 Oct 22;172(19):1484 , editorial can be found in Arch Intern
Med 2012 Oct 22;172(19):1492

Evaluation for obscure gastrointestinal bleeding

● see Acute Lower Gastrointestinal Bleeding in Adults, section on evaluation and treatment of obscure
gastrointestinal bleeding

Complications and Prognosis

Complications

● hypovolemic shock

● iron de ciency anemia (more likely with chronic bleeding)

Prognosis

Mortality

● 30-day mortality up to 11% reported 2

STUDY
● SUMMARY
risk of mortality may vary by source of nonvariceal upper gastrointestinal (GI) bleeding

COHORT STUDY: Gastrointest Endosc 2012 Feb;75(2):263

Details
⚬ based on cohort study
⚬ 3,207 patients (mean age 68.3 years) with acute upper GI bleeding were reviewed
⚬ overall mortality 4.45% (143 patients)
⚬ mortality by source of upper GI bleeding

– 9.8% for neoplasia

– 4.8% for Mallory-Weiss tears
– 4.8% for vascular lesions
– 4.4% for gastroduodenal erosions
– 4.4% for duodenal ulcer
– 3.1% for gastric ulcer

⚬ Reference - Gastrointest Endosc 2012 Feb;75(2):263

● weekend admission associated with increased in-hospital or 30-day mortality compared to weekday
admission in patients with nonvariceal upper gastrointestinal bleeding but not in patients with
variceal upper gastrointestinal bleeding in systematic review of 21 observational studies with 711,650
 patients with upper gastrointestinal (GI) bleeding (Am J Gastroenterol 2018 Jan;113(1):13 ); similar
results in systematic review of 18 observational studies with 1,232,083 patients (PeerJ 2018;6:e4248
full-text )

STUDY
● SUMMARY
inpatients with acute upper GI bleed appear sicker and at higher risk of death than patients who
start upper GI bleed as outpatient

COHORT STUDY: Gastrointest Endosc 2014 May;79(5):741

Details
⚬ based on retrospective cohort study
⚬ 2,317 patients with acute nonvariceal upper GI bleeding having endoscopic treatment within 24
hours of acute bleed were reviewed
– 333 patients started bleeding while an inpatient for another condition
– 1,979 patients started bleeding as an outpatient

⚬ comparing patients who started bleeding as an inpatient vs. outpatient

– mortality 8.9% vs. 3.8% (p < 0.001)

– death from bleeding-related causes 4.1% vs. 1.1% (p < 0.001)
– severity of comorbid diseases (American Society of Anesthesiologists class 3-4) 44.9% vs. 24.6%
– on steroids 14.2% vs. 5%
– on heparin 17.7% vs. 3.5%

⚬ Reference - Gastrointest Endosc 2014 May;79(5):741

STUDY
● SUMMARY
elevated lactate levels may have high specificity but low sensitivity for predicting hypotension
within 24 hours in normotensive patients with acute nonvariceal upper gastrointestinal bleeding
in emergency department DynaMed Level 2

PREDICTION RULE: Crit Care Med 2015 Nov;43(11):2409

Details
⚬ based on prognostic cohort study without independent validation
⚬ 1,003 normotensive patients (mean age 62 years, 73% men) presenting to emergency department
with acute nonvariceal upper gastrointestinal bleeding were assessed for blood lactate levels and
monitored for hypotension
⚬ patients excluded for cirrhosis or advanced malignancy
⚬ in-hospital hypotension within 24 hours (systolic blood pressure < 90 mm Hg) developed in 15.7%
⚬ 30-day mortality was 3.1%
⚬ prognostic performance of lactate level with cuto ≥ 2.5 mmol/L
– for predicting in-hospital hypotension within 24 hours

● sensitivity 35%
● speci city 90%
● positive predictive value 48%
● negative predictive value 84%

– for predicting 30-day mortality

● sensitivity 81%
 ● speci city 81%
● positive predictive value 12%
● negative predictive value 99%

⚬ Reference - Crit Care Med 2015 Nov;43(11):2409 , editorial can be found in Crit Care Med 2015
Nov;43(11):2511

STUDY
● SUMMARY
diabetes associated with increased 30-day mortality in patients with bleeding or perforated
peptic ulcer

COHORT STUDY: Diabetes Care 2006 Apr;29(4):805

Details
⚬ based on retrospective cohort study
⚬ cohort of 7,232 patients hospitalized for bleeding ulcers

– 731 (10%) had diabetes

– diabetes associated with higher 30-day mortality (16.6% vs. 10.1%, adjusted rate ratio 1.4 [95%
CI 1.15-1.7])
⚬ cohort of 2,061 patients hospitalized for perforated ulcers

– 140 (7%) had diabetes

– diabetes associated with higher 30-day mortality (42.9% vs. 24%, adjusted rate ratio 1.5 [95% CI
1.15-1.98])
⚬ Reference - Diabetes Care 2006 Apr;29(4):805

Risk of recurrent hemorrhage

STUDY
● SUMMARY
overall risk of recurrent hemorrhage may be about 16% after endoscopic hemostatic therapy for
bleeding peptic ulcers

SYSTEMATIC REVIEW: Am J Gastroenterol 2008 Oct;103(10):2625

Details
⚬ based on systematic review with inconsistent evidence
⚬ systematic review of 10 prospective studies assessing rebleeding after endoscopic therapy for
bleeding peptic ulcers
⚬ initial hemostasis achieved in 92.3%
⚬ pooled rebleeding rate 16.4%
⚬ overall mortality 6.4%
⚬ pre-endoscopic risk factors for rebleeding

– hemodynamic instability (signi cant in 5 of 5 studies)

– comorbid illness (signi cant in 2 of 7 studies)

⚬ endoscopic risk factors for rebleeding

– active bleeding at endoscopy (signi cant in 5 of 8 studies)

– large ulcer size (signi cant in 4 of 5 studies)
– posterior duodenal ulcer (signi cant in 2 of 3 studies)
– lesser gastric curvature ulcer (signi cant in 2 of 2 studies)
 ⚬ Reference - Am J Gastroenterol 2008 Oct;103(10):2625

● Forrest classi cation of ulcers may inform risk for rebleeding

Table 7. Forrest Criteria for Grading Ulcers

Forrest Class Type of Lesion Reported Risk of

Rebleeding if Untreated

IA Arterial spurting 100%

bleeding

IB Arterial oozing bleeding 55%

IIA Visible vessel 43%

IIB Sentinel clot 22%

IIC Hematin-covered at 10%

spot

III No stigmata of 5%
hemorrhage

Reference - Lancet 1974 Aug 17;2(7877):394 .

STUDY
● SUMMARY
INR at presentation not associated with risk of rebleeding in patients with nonvariceal upper GI
bleeding

COHORT STUDY: Aliment Pharmacol Ther 2011 May;33(9):1010

Details
⚬ based on retrospective cohort study
⚬ 1,869 patients who had endoscopy for nonvariceal upper GI bleeding were analyzed
⚬ no signi cant association between INR and risk of rebleeding
⚬ predictors of mortality include

– rebleeding (odds ratio 4.88, 95% CI 2.85-8.35)

– bright blood on rectal examination (odds ratio 2.59, 95% CI 1.49-4.5)
– bright red blood or blood with co ee ground appearance in nasogastric tube aspirate (odds
ratio 2.09, 95% CI 1.21-3.62)
– INR ≥ 1.5 (odds ratio 1.96, 95% CI 1.13-3.41)

⚬ Reference - Aliment Pharmacol Ther 2011 May;33(9):1010

Risk of readmission

STUDY
● SUMMARY
higher Charlson Comorbidity Index, hemorrhagic shock, longer length of stay, and Medicaid
insurance during initial hospitalization associated with increased risk of readmission within 30
days in patients with acute nonvariceal upper gastrointestinal bleeding

COHORT STUDY: Gastroenterology 2018 Jul;155(1):38

Details
⚬ based on retrospective cohort study
⚬ 203,220 adults (mean age 66 years) who were hospitalized for acute nonvariceal upper
gastrointestinal bleeding were evaluated for readmission within 30 days
– during initial hospitalization, endoscopy in 86.2%, endoscopic therapy in 25.4%, and rescue
embolization therapy in < 2%
– 98.1% discharged from hospital alive

⚬ 13% had readmission within 30 days overall

⚬ 18.5% of readmissions due to rebleeding
⚬ factors associated with increased risk of readmission within 30 days include

– higher Charlson Comorbidity Index (per additional point odds ratio [OR] 1.14, 95% CI 1.13-1.16)
– hemorrhagic shock during initial hospitalization (OR 1.14, 95% CI 1.04-1.24)
– length of initial hospital stay (per additional day OR 1.02, 95% CI 1.01-1.02)
– Medicaid insurance (compared to Medicare) (OR 1.19, 95% CI 1.1-1.29)

⚬ factors associated with reduced risk of readmission within 30 days include

– endoscopy during initial hospitalization (OR 0.75, 95% CI 0.71-0.79)

– prolonged mechanical ventilation during initial hospitalization (OR 0.7, 95% CI 0.54-0.9)
– private insurance (compared to Medicare) (OR 0.66, 95% CI 0.62-0.72)
– no insurance (compared to Medicare) (OR 0.68, 95% CI 0.61-0.75)

⚬ Reference - Gastroenterology 2018 Jul;155(1):38

Prevention

Primary prevention of acute nonvariceal upper gastrointestinal hemorrhage

Primary prevention in noncritically ill patients

● for patients on nonsteroidal anti-in ammatory drugs (NSAIDs) long-term

⚬ risk of NSAID-induced endoscopic gastric and duodenal ulcers can be reduced by

– proton pump inhibitors (PPIs) (also reduce NSAID-induced dyspepsia)

– misoprostol
– double-dose histamine-2 (H2) blockers

⚬ misoprostol reduces bleeding, perforation, or gastric outlet obstruction from NSAID-induced

ulcers, but poorly tolerated
⚬ Reference - Health Technol Assess 2007 Dec;11(51):1

⚬ see also Prevention of NSAID-induced Gastrointestinal Toxicity

STUDY
● SUMMARY
in hospitalized noncritically ill patients, acid-suppressive medications appear to have limited
efficacy for preventing nosocomial upper gastrointestinal bleeding DynaMed Level 2

COHORT STUDY: Arch Intern Med 2011 Jun 13;171(11):991 | Full Text

Details
⚬ based on cohort of 78,394 adult patients (median age 56 years, 41% male) admitted to hospital for
≥ 3 days for diagnoses other than upper gastrointestinal bleeding
⚬ 59% had acid-suppressive medication (PPI or histamine-2-receptor antagonist)
⚬ 0.29% (224 patients) had nosocomial upper gastrointestinal bleeding
⚬ patients were propensity-matched to control for confounding factors
⚬ in propensity-matched analysis, acid suppressive medication associated with reduced incidence of

– nosocomial upper gastrointestinal bleeding (odds ratio [OR] 0.63, 95% CI 0.42-0.93, NNT 770)
– clinically signi cant upper gastrointestinal bleeding (OR 0.58, 95% CI 0.31-0.91, NNT 834)

⚬ Reference - Arch Intern Med 2011 Jun 13;171(11):991 full-text

STUDY
● SUMMARY
use of standardized guidelines during hospital admission may reduce new use of PPIs for
prevention of nosocomial upper gastrointestinal bleeding DynaMed Level 2

BEFORE AND AFTER STUDY: Arch Intern Med 2010 May 10;170(9):779 | Full Text

Details
⚬ based on before-and-after study
⚬ 942 inpatients (mean age 63 years, 58% men) were evaluated for PPI prescription and use 1 month
before and 1 month after implementation of standardized guidelines for PPI use
⚬ 36.2% were taking PPIs at admission
⚬ guidelines for PPI use for prophylaxis of nosocomial upper gastrointestinal bleeding were
developed based on systematic review of retrospective and prospective studies
– PPI orally or enterally once daily indicated for

● patients in intensive care unit with coagulopathy

● patients requiring mechanical ventilation

– PPI orally or enterally once daily to be considered for patients with history of peptic ulcer
disease (particularly if receiving NSAID or antiplatelet therapy)
– IV PPI not indicated

⚬ comparing before PPI guideline vs. after PPI guideline in analysis of 601 patients not taking PPI at
admission
– PPI use as inpatient in 27.2% vs. 16.3% (p = 0.001, NNT 10)
– PPI use at discharge in 16% vs. 10.1% (p = 0.03, NNT 17)

⚬ Reference - Arch Intern Med 2010 May 10;170(9):779 full-text , editorial can be found in Arch
Intern Med 2010 May 10;170(9):747 , Arch Intern Med 2010 May 10;170(9):749

Primary prevention in critically ill patients

● options for prophylaxis include

⚬ histamine-2 (H2) receptor antagonists

– H2 receptor antagonists may reduce risk of gastrointestinal bleeding in most patients, but e ect
on mortality is inconsistent
 – in critically ill patients receiving enteral nutrition, H2 blockers may not reduce bleeding risk and
may increase mortality and risk of nosocomial pneumonia
⚬ sucralfate appears to have similar reductions in gastrointestinal bleeding as H2 receptor
antagonists and might reduce risk of pneumonia
⚬ proton pump inhibitors may reduce gastrointestinal bleeding compared to H2 receptor
antagonists in critically ill patients
⚬ enteral nutrition (EN)

– EN is often part of routine care for critically ill patients and no randomized trials have compared
EN alone vs. acid-suppressive therapy alone
– many patients receiving EN may not require acid-suppressive prophylaxis, but EN alone may be
insu cient in certain patient including those with burns, head injury, or over bleeding
– addition of H2 blockers or other acid-suppressive prophylaxis may increase risk of
gastrointestinal bleeding in critically ill patients

● see also Acute Gastritis Prophylaxis in Critically Ill Patients

Secondary prevention of acute nonvariceal upper gastrointestinal hemorrhage

● in patients with previous ulcer bleeding who require nonsteroidal anti-in ammatory drugs (NSAIDs),
use combination of proton-pump inhibitor (PPI) and cyclooxygenase-2 (COX-2) inhibitor at lowest
e ective dose to reduce risk of rebleeding (ICUGB Grade 1B; ACG Strong recommendation) 2 , 4

● Helicobacter pylori eradication reduces rebleeding rates following peptic ulcer bleeding compared to
antisecretory therapy alone (Health Technol Assess 2007 Dec;11(51):1 )

STUDY
● SUMMARY
Helicobacter pylori eradication therapy appears more effective than short-term antisecretory
therapy or long-term ranitidine in preventing recurrent peptic ulcer bleeding DynaMed Level 2

in patients not taking long-term nonsteroidal anti-inflammatory drugs (NSAIDs)

COCHRANE REVIEW: Cochrane Database Syst Rev 2004;(2):CD004062

Details
⚬ based on Cochrane review of trials without blinding
⚬ systematic review of 10 controlled trials with 1,048 patients comparing H. pylori eradication therapy
vs. antisecretory noneradication therapy (with or without long-term maintenance antisecretory
therapy) for prevention of recurrent bleeding from peptic ulcer
⚬ no trials were double-blind
⚬ trials were excluded if no previous upper gastrointestinal bleeding or if all patients received NSAIDs
⚬ 8 trials included only patients with duodenal ulcers
⚬ 7 trials with 578 patients compared H. pylori eradication therapy vs. antisecretory noneradication
therapy without subsequent long-term maintenance antisecretory therapy
– short-term antisecretory therapy was omeprazole in 4 trials, ranitidine in 1 trial, histamine-2
(H2) antagonist plus antacids in 1 trial, and bismuth in 1 trial
– eradication therapy associated with lower rate of recurrent bleeding (odds ratio 0.17, 95% CI
0.1-0.32)
– NNT 7 (95% CI 5-11)

⚬ 3 trials with 470 patients compared H. pylori eradication therapy vs. long-term maintenance
antisecretory therapy
 – antisecretory maintenance therapy was ranitidine in 2 trials, and ranitidine or omeprazole in 1
trial
– eradication therapy associated with lower rate of recurrent bleeding (odds ratio 0.24, 95% CI
0.09-0.67)
– NNT 20 (95% CI 12-100)

⚬ Cochrane review authors do not plan on updating this review (review updated 2010 Sep 20 with no
new trials)
⚬ Reference - Cochrane Database Syst Rev 2004;(2):CD004062

STUDY
● SUMMARY
Helicobacter pylori eradication therapy may be less effective than daily omeprazole for preventing
recurrent bleeding in patients who continue long-term nonsteroidal anti-inflammatory drugs
(NSAIDs) after treatment for bleeding peptic ulcer DynaMed Level 2

RANDOMIZED TRIAL: N Engl J Med 2001 Mar 29;344(13):967

Details
⚬ based on randomized trial without complete blinding
⚬ 400 patients who were treated for bleeding peptic ulcer had H. pylori infection, and had con rmed
healing of ulcer after 8 weeks of omeprazole therapy were randomized to H. pylori eradication
therapy vs. continued omeprazole 20 mg once daily for 6 months
– eradication therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, plus metronidazole 400
mg) given 4 times daily for 1 week
– eradication therapy group received placebo instead of daily omeprazole, but omeprazole group
did not receive placebo for eradication regimen
⚬ all patients given long-term NSAIDs of some type

– aspirin 80 mg orally once daily for coronary heart disease or stroke (250 patients)
– naproxen 500 mg orally twice daily for arthritis (150 patients)

⚬ recurrent upper gastrointestinal bleeding de ned as signs of bleeding (hematemesis or melena or

decrease in hemoglobin by 2 g/dL [20 g/L]) plus ulcers or bleeding erosion con rmed on endoscopy
⚬ comparing eradication therapy vs. continued omeprazole

– among 250 patients taking low-dose aspirin, recurrent bleeding in 1.9% vs. 0.9% (not signi cant)
– among 150 patients taking other NSAIDs, recurrent bleeding in 18.8% vs. 4.4% (p = 0.005, NNT 7
favoring continued omeprazole)
⚬ Reference - N Engl J Med 2001 Mar 29;344(13):967 , commentary can be found in N Engl J Med
2001 Jul 5;345(1):67

STUDY
● SUMMARY
maintenance antisecretory therapy may not be necessary after Helicobacter pylori eradication in
patients with bleeding peptic ulcers DynaMed Level 2

RANDOMIZED TRIAL: Arch Intern Med 2003 Sep 22;163(17):2020 | Full Text

Details
⚬ based on randomized trial with inadequate description of blinding
⚬ 99 patients with H. pylori-associated bleeding peptic ulcers were treated with 1-week eradication
therapy then omeprazole 20 mg once daily for 3 more weeks for ulcer healing
⚬ 78 patients had duodenal ulcers, 11 patients had gastric ulcers
 ⚬ 82 patients were then randomized to 1 of 4 regimens for 16 weeks

– antacid 15 mL 4 times daily

– colloidal bismuth subcitrate 300 mg 4 times daily
– famotidine 20 mg twice daily
– placebo twice daily

⚬ mean follow-up 56 months

⚬ 38 patients had endoscopy for ulcer-like symptoms, none had peptic ulcer recurrence or H. pylori
reinfection
⚬ Reference - Arch Intern Med 2003 Sep 22;163(17):2020 full-text

Guidelines and Resources

Guidelines

International guidelines

● World Society of Emergency Surgery (WSES) guideline on perforated and bleeding peptic ulcer can be
found in World J Emerg Surg 2020;15:3

● International Consensus Group (ICG) guideline on management of nonvariceal upper gastrointestinal

bleeding can be found in Ann Intern Med 2019 Dec 3;171(11):805

● Asia-Paci c working group consensus on nonvariceal upper gastrointestinal bleeding can be found in
Gut 2018 Oct;67(10):1757 full-text , correction can be found in Gut 2019 Feb;68(2):380

● International Consensus Upper Gastrointestinal Bleeding (ICUGB) Conference Group recommendation

on management of patients with nonvariceal upper gastrointestinal bleeding can be found in Ann
Intern Med 2019 Oct 22 early online
⚬ previous version can be found in Ann Intern Med 2010 Jan 19;152(2):101

United States guidelines

● American College of Gastroenterology (ACG) guidelines on

⚬ management of patients with ulcer bleeding can be found in Am J Gastroenterol 2012

Mar;107(3):345 , commentary can be found in Am J Gastroenterol 2012 Oct;107(10):1590
⚬ diagnosis and management of small bowel bleeding can be found in Am J Gastroenterol 2015
Sep;110(9):1265

● American Society for Gastrointestinal Endoscopy (ASGE) guidelines on

⚬ role of endoscopy in management of acute nonvariceal upper gastrointestinal bleeding can be

found in Gastrointest Endosc 2012 Jun;75(6):1132
⚬ role of endoscopy in management of patients with peptic ulcer disease can be found in
Gastrointest Endosc 2010 Apr;71(4):663
⚬ modi cations in endoscopic practice for the elderly can be found in Gastrointest Endosc 2013
Jul;78(1):1
⚬ adverse events of upper gastrointestinal (GI) endoscopy can be found in Gastrointest Endosc 2012
Oct;76(4):707
⚬ antibiotic prophylaxis for GI endoscopy can be found in Gastrointest Endosc 2015 Jan;81(1):81
 ⚬ infection control during gastrointestinal endoscopy can be found in Gastrointest Endosc 2018
May;87(5):1167

● multisociety guideline on reprocessing exible GI endoscopes can be found in Gastrointest Endosc

2017 Feb;85(2):282

● American College of Radiology (ACR) Appropriateness Criteria for nonvariceal upper gastrointestinal
bleeding can be found in J Am Coll Radiol 2017 May;14(5S):S177 or at ACR 2016 PDF

● American College of Cardiology Foundation/American College of Gastroenterology/American Heart

Association (ACCF/ACG/AHA) expert consensus document on reducing gastrointestinal risks of
antiplatelet therapy and nonsteroidal anti-in ammatory drug use can be found in Circulation 2008
Oct 28;118(18):1894 , correction can be found in Circulation 2010 Aug 24;122(8):e438, also
published in Am J Gastroenterol 2008 Nov;103(11):2890
⚬ ACCF/ACG/AHA expert consensus document on concomitant use of proton pump inhibitors and
thienopyridines can be found in J Am Coll Cardiol 2010 Dec 7;56(24):2051 full-text , Circulation
2010 Dec 14;122(24):2619 , and Am J Gastroenterol 2010 Dec;105(12):2533

United Kingdom guidelines

● National Institute for Health and Care Excellence (NICE) guideline on management of acute upper
gastrointestinal bleeding in over 16s can be found at NICE 2012 Jun:CG141 PDF , updated 2016
Aug 25, summary can be found in BMJ 2012 Jun 13;344:e3412

European guidelines

● European Society of Gastrointestinal Endoscopy (ESGE)

⚬ ESGE cascade guideline on nonvariceal upper gastrointestinal hemorrhage can be found in Endosc
Int Open 2018 Oct;6(10):E1256
⚬ ESGE guideline on diagnosis and management of nonvariceal upper gastrointestinal bleeding can
be found in Endoscopy 2015 Oct;47(10):a1 full-text

● European Association for the Study of the Liver (EASL) clinical guideline on management of ascites,
spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis can be found in J Hepatol
2010 Sep;53(3):397 full-text

● Italian Society of Gastroenterology (SIGE) position paper on pharmacological treatment of

gastrointestinal bleeding due to angiodysplasias can be found in Dig Liver Dis 2018 Jun;50(6):542

Asian guidelines

● Japan Gastroenterological Endoscopy Society (JGES) guideline on endoscopic management of

nonvariceal upper gastrointestinal bleeding can be found in Dig Endosc 2016 May;28(4):363

● Chinese Journal of Internal Medicine, National Medical Journal of China, Chinese Journal of Digestion,
and Chinese Journal of Digestive Endoscopy (CJIM/NMJC/CJD/CJDE) guideline on diagnosis and
treatment of acute nonvariceal upper gastrointestinal bleeding can be found in J Dig Dis 2016
Feb;17(2):79

Middle Eastern guidelines

● Israel Gastroenterology Association (IGA) guideline on use of video capsule endoscopy in diseases of
small bowel, esophagus, and colon can be found in Harefuah 2011 Oct;150(10):806 [Hebrew]

Review articles

● reviews can be found in

⚬ Nat Rev Dis Primers 2018 Apr 19;4:18020

⚬ Crit Care Clin 2016 Apr;32(2):223

⚬ Curr Opin Crit Care 2015 Apr;21(2):154

● reviews of acute upper (nonvariceal and variceal) gastrointestinal bleeding can be found in

⚬ BMJ 2019 Mar 25;364:l536

⚬ J R Coll Physicians Edinb 2017 Sep;47(3):218
Edinb 2017 Dec;47(4):397
⚬ Ann Intern Med 2013 Aug 6;159(3):ITC2
3;159(11):793
⚬ Frontline Gastroenterol 2016 Jan;7(1):32
, commentary can be found in J R Coll Physicians
, commentary can be found in Ann Intern Med 2013 Dec
full-text

● review of upper gastrointestinal bleeding in adults can be found in Am Fam Physician 2020 Mar
1;101(5):294

● review of upper gastrointestinal bleeding due to peptic ulcer can be found in N Engl J Med 2016 Jun
16;374(24):2367 , commentary can be found in N Engl J Med 2016 Sep 22;375(12):1198

● review of upper gastrointestinal bleeding risk scores can be found in World J Gastrointest
Pathophysiol 2016 Feb 15;7(1):86 full-text

● reviews of diagnosis and management can be found in

⚬ Dis Mon 2018 Jul;64(7):333

⚬ World J Gastrointest Pharmacol Ther 2015 Nov 6;6(4):172 full-text

● review of diagnosis and management of upper gastrointestinal bleeding can be found in Am Fam
Physician 2012 Mar 1;85(5):469 full-text

● review of management of bleeding from peptic ulcer can be found in F1000Res 2017 Sep 27;6:1763

full-text

● reviews of endoscopic techniques for hemostasis can be found in

⚬ Frontline Gastroenterol 2015 Apr;6(2):147 full-text

⚬ World J Gastrointest Endosc 2016 Feb 25;8(4):205 full-text

● review of endoscopic treatment of peptic ulcer bleeding can be found in Clin Endosc 2016
Sep;49(5):417 full-text

● review of prophylaxis against upper gastrointestinal bleeding in hospitalized patients can be found in
N Engl J Med 2018 Jun 28;378(26):2506
● review of occult and obscure gastrointestinal bleeding can be found in Nat Rev Gastroenterol Hepatol
2010 May;7(5):265

● review of evaluation of occult gastrointestinal bleeding can be found in Am Fam Physician 2013 Mar
15;87(6):430 full-text

● review of imaging for investigating occult gastrointestinal hemorrhage can be found in BMJ 2008 Jul
3;337:a422 full-text

MEDLINE search

● to search MEDLINE for (Acute upper gastrointestinal bleeding) with targeted search (Clinical Queries),
click therapy , diagnosis , or prognosis

Patient Information

● handouts from EBSCO Health Library on

⚬ gastrointestinal bleeding or in Spanish

⚬ peptic ulcer or in Spanish

● handout on bleeding in the digestive tract from National Institute of Diabetes and Digestive and
Kidney Diseases or in Spanish

● handout on upper GI bleeding in children from GI Kids PDF , or in Spanish PDF or French PDF

ICD Codes

ICD-10 codes

● I85.0 oesophageal varices with bleeding

● K22.6 gastro-oesophageal laceration-haemorrhage syndrome

● K22.8 other speci ed diseases of oesophagus

● K25 gastric ulcer

⚬ K25.0 gastric ulcer, acute with haemorrhage

⚬ K25.2 gastric ulcer, acute with both haemorrhage and perforation
⚬ K25.4 gastric ulcer, chronic or unspeci ed with haemorrhage
⚬ K25.6 gastric ulcer, chronic or unspeci ed with both haemorrhage and perforation

● K26 duodenal ulcer

⚬ K26.0 duodenal ulcer, acute with haemorrhage

⚬ K26.2 duodenal ulcer, acute with both haemorrhage and perforation
⚬ K26.4 duodenal ulcer, chronic or unspeci ed with haemorrhage
⚬ K26.6 duodenal ulcer, chronic or unspeci ed with both haemorrhage and perforation

● K27 peptic ulcer, site unspeci ed

⚬ K27.0 peptic ulcer, site unspeci ed, acute with haemorrhage

⚬ K27.2 peptic ulcer, site unspeci ed, acute with both haemorrhage and perforation
 ⚬ K27.4 peptic ulcer, site unspeci ed, chronic or unspeci ed with haemorrhage
⚬ K27.6 peptic ulcer, site unspeci ed, chronic or unspeci ed with both haemorrhage and perforation

● K28 gastrojejunal ulcer

⚬ K28.0 gastrojejunal ulcer, acute with haemorrhage

⚬ K28.2 gastrojejunal ulcer, acute with both haemorrhage and perforation
⚬ K28.4 gastrojejunal ulcer, chronic or unspeci ed with haemorrhage
⚬ K28.6 gastrojejunal ulcer, chronic or unspeci ed with both haemorrhage and perforation

● K29.0 acute haemorrhagic gastritis

● K92.0 haematemesis

● K92.1 melaena

● K92.2 gastrointestinal haemorrhage, unspeci ed

References

General references used

1. Scottish Intercollegiate Guidelines Network (SIGN). Management of acute upper and lower
gastrointestinal bleeding: A national clinical guideline. SIGN 2008 Sep:105 , summary can be found
in BMJ 2008 Oct 10;337:a1832

2. Barkun AN, Almadi M, Kuipers EJ, et al. Management of Nonvariceal Upper Gastrointestinal Bleeding:
Guideline Recommendations From the International Consensus Group. Ann Intern Med. 2019 Oct 22
early online , and previous version can be found in Ann Intern Med 2010 Jan 19;152(2):101 ,
commentary can be found in Rev Clin Esp 2010 Sep;210(8):410

3. Wilkins T, Khan N, Nabh A, Schade RR. Diagnosis and management of upper gastrointestinal bleeding.
Am Fam Physician. 2012 Mar 1;85(5):469-76 full-text

4. Laine L, Jensen DM, American College of Gastroenterology. Management of patients with ulcer
bleeding. Am J Gastroenterol. 2012 Mar;107(3):345-60 , commentary can be found in Am J
Gastroenterol 2012 Oct;107(10):1590

5. Klein A, Gralnek IM. Acute, nonvariceal upper gastrointestinal bleeding. Curr Opin Crit Care. 2015
Apr;21(2):154-62

6. Gralnek IM, Dumonceau JM, Kuipers EJ, et al. Diagnosis and management of nonvariceal upper
gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
Endoscopy. 2015 Oct;47(10):a1-46 full-text

Recommendation grading systems used

● European Society of Gastrointestinal Endoscopy (ESGE) uses Grading of Recommendations,

Assessment, Development, and Evaluation (GRADE) system
⚬ strength of recommendation
 – Strong recommendation - desirable e ects of an intervention clearly outweigh the undesirable
e ects
– Weak recommendation - uncertainty about trade-o s between desirable and undesirable
e ects of an intervention
⚬ quality of evidence

– High-quality evidence - further research unlikely to change con dence in estimate of e ect
– Moderate-quality evidence - further research likely to have impact on con dence in estimate of
e ect
– Low-quality evidence - further research very likely to have important impact on con dence in
estimate of e ect and is likely to change estimate
– Very low-quality evidence - estimate of e ect very uncertain

⚬ Reference - ESGE guideline on diagnosis and management of nonvariceal upper gastrointestinal

hemorrhage (Endoscopy 2015 Oct;47(10):a1 full-text )

● American College of Gastroenterology (ACG) grading system for recommendations

⚬ strength of recommendation

– Strong recommendation - desirable e ects of intervention clearly outweigh undesirable e ects

– Conditional recommendation - uncertainty over whether desirable e ects of intervention
outweigh undesirable e ects
⚬ quality of evidence

– High-quality evidence - further research very unlikely to change con dence in estimate of e ect
– Moderate-quality evidence - further research likely to have important impact on con dence in
estimate of e ect; estimate may change
– Low-quality evidence - further research very likely to have important impact on con dence in
estimate of e ect; estimate will likely change
– Very low-quality evidence - any estimate of e ect very uncertain

⚬ Reference - ACG practice guideline on management of patients with ulcer bleeding (Am J
Gastroenterol 2012 Mar;107(3):345 ), commentary can be found in Am J Gastroenterol 2012
Oct;107(10):1590

● Scottish Intercollegiate Guidelines Network (SIGN) de nitions of grades of recommendation and levels
of evidence
⚬ grades of recommendations

– Grade A

● at least 1 meta-analysis, systematic review, or randomized controlled trial (RCT) rated as 1++
and directly applicable to the target population, or
● body of evidence consisting principally of studies rated as 1+, directly applicable to target
population and demonstrating overall consistency of results
– Grade B

● body of evidence including studies rated as 2++, directly applicable to target population and
demonstrating overall consistency of results, or
● extrapolated evidence from studies rated as 1++ or 1+

– Grade C

● body of evidence including studies rated as 2+, directly applicable to target population and
demonstrating overall consistency of results, or
● extrapolated evidence from studies rated as 2++
 – Grade D

● evidence level 3 or 4, or
● extrapolated evidence from studies rated as 2+

– Good Practice Point - recommended best practice based on clinical experience of guideline
development group
⚬ levels of evidence

– 1++ - high-quality meta-analyses, systematic reviews of RCTs, or RCTs with very low risk of bias
– 1+ - well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with low risk of bias

– 1- - meta-analyses, systematic reviews of RCTs, or RCTs with high risk of bias

– 2++

● high-quality systematic reviews of case-control or cohort studies

● high-quality case-control or cohort studies with very low risk of confounding or bias and high
probability that relationship is causal
– 2+ - well-conducted case-control or cohort studies with low risk of confounding or bias and
moderate probability that relationship is causal
– 2- - case-control or cohort studies with high risk of confounding or bias and signi cant risk that
relationship is not causal
– 3 - nonanalytical studies (for example, case reports, case series)
– 4 - expert opinion

⚬ Reference - SIGN national clinical guideline on management of acute upper and lower
gastrointestinal bleeding (SIGN 2008 Sep:105 PDF )

● International Consensus Upper Gastrointestinal Bleeding (ICUGB) Conference Group 2019 grading
system for recommendations
⚬ strength of recommendation

– Strong recommendation - desirable e ects of intervention clearly outweigh undesirable e ects

– Conditional recommendation - uncertainty over whether desirable e ects of intervention
outweigh undesirable e ects
⚬ quality of evidence

– High-quality evidence - further research very unlikely to change con dence in estimate of e ect
– Moderate-quality evidence - further research likely to have important impact on con dence in
estimate of e ect; estimate may change
– Low-quality evidence - further research very likely to have important impact on con dence in
estimate of e ect; estimate will likely change
– Very low-quality evidence - any estimate of e ect very uncertain

⚬ Reference - ICUGB recommendations on management of patients with nonvariceal upper

gastrointestinal bleeding (Ann Intern Med 2019 Oct 22 early online )

● International Consensus Upper Gastrointestinal Bleeding (ICUGB) Conference Group 2010 grading
system for recommendations
⚬ Grade 1A - Strong recommendation, high-quality evidence

– desirable e ects clearly outweigh undesirable e ects or vice versa

– consistent evidence from randomized controlled trials (RCTs) without important limitations or
exceptionally strong evidence from observational studies
⚬ Grade 1B - Strong recommendation, moderate-quality evidence
 – desirable e ects clearly outweigh undesirable e ects or vice versa
– evidence from RCTs with important limitations (inconsistent results, methodologic aws,
indirect or imprecise), or very strong evidence from observational studies
⚬ Grade 1C - Strong recommendation, low- or very low-quality evidence

– desirable e ects clearly outweigh undesirable e ects or vice versa

– evidence from at least 1 critical outcome from observational studies, case series, or from RCTs
with serious aws or indirect evidence
⚬ Grade 2A - Weak recommendation, high-quality evidence

– desirable e ects closely balanced with undesirable e ects

– consistent evidence from RCTs without important limitations or exceptionally strong evidence
from observational studies
⚬ Grade 2B - Weak recommendation, moderate-quality evidence

– desirable e ects closely balanced with undesirable e ects

– evidence from RCTs with important limitations (inconsistent results, methodologic aws,
indirect or imprecise), or very strong evidence from observational studies
⚬ Grade 2C - Weak recommendation, low- or very low-quality evidence

– desirable e ects closely balanced with undesirable e ects

– evidence from at least 1 critical outcome from observational studies, case series, or from RCTs
with serious aws or indirect evidence
⚬ Reference - ICUGB recommendations on management of patients with nonvariceal upper
gastrointestinal bleeding (Ann Intern Med 2010 Jan 19;152(2):101 ), commentary can be found in
Rev Clin Esp 2010 Sep;210(8):410 [Spanish]

● Canadian Association of Gastroenterology (CAG) GERD Consensus Group

⚬ classi cation of recommendations

– A - good evidence to support procedure or treatment

– B - fair evidence to support procedure or treatment
– C - poor evidence to support procedure or treatment, but recommendations may be made on
other grounds
– D - fair evidence that procedure or treatment should not be used
– E - good evidence that procedure or treatment should not be used

⚬ quality of evidence

– I - evidence obtained from ≥ 1 properly randomized controlled trial

– II-1 - evidence obtained from well-designed controlled trials without randomization
– II-2 - evidence obtained from well-designed cohort or case-control analytic studies, preferably
from > 1 centre or research group
– II-3 - evidence obtained from comparisons between times or places with or without the
intervention, or dramatic results in uncontrolled experiments
– III - opinions of respected authorities, based on clinical experience, descriptive studies or
reports of expert committees
⚬ Reference - CAG Canadian Consensus Conference 2004 guideline on management of
gastroesophageal re ux disease in adults (Can J Gastroenterol 2005 Jan;19(1):15 )

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⚬ Strong recommendations are used when, based on the available evidence, clinicians (without
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On behalf of the American College of Physicians

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