GI BLEEDING
| GI BLEEDING AND HOW TO CONTROL IT —Jeffrey Marks, MD, Assistant Professor of Surgery, Case Western Reserve
University School of Medicine, University Hospitals of Cleveland, Cleveland, OH
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| Introduction: gastrointestinal (GI) bleeding one of most common medical emergencies (although not one of most common
surgical emergencies); histamine (H)2 blockers and proton pump inhibitors (PPIs) changed face of GI surgery; upper GI
bleeding more common than lower GI bleeding (resolves in 80%-90% of cases)
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| Upper GI bleeding: mortality rate almost 10%; comorbid diseases increase mortality rate; accounts for ≈20,000 deaths annually;
important to have collaborative team approach (endoscopist, surgeon, and clinical pathway); GI bleeding ranges
from heme-positive stools to massive rectal bleeding; accounts for 10% of cases of iron deficiency anemia; initial
assessment—determine rapidity of bleeding; hematemesis and melena most common; takes <2 mL of blood to cause
melena; blood good cathartic (gets to distal colon quickly and causes hematochezia); obtain careful history of whether
patient has comorbid diseases (eg, underlying renal or hepatic disease that could predispose to varices, platelet dysfunction,
Mallory-Weiss tear [vomiting, coughing, alcohol abuse], tumors)
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| Endoscopic intervention: preparation of patient most important; choice of tools; determining where patient should be prepared
(emergency department [ED], intensive care unit [ICU], or floor); laboratory work-up—in correcting coagulopathy,
if international normalized ratio (INR) >1.5, chance of stopping bleeding <30%; those with renal disease and platelet
dysfunction may require desmopressin (DDAVP); bleeding team—having good interventional radiologist and intensivist
reduces mortality by one-third; acid suppression key factor; rebleeding rates without PPIs 3 times higher; if evidence that
patient is high-risk bleeder, give intravenous (IV) PPI; gold standard 80-mg bolus followed by IV infusion (usually 24-36
hr, up to 72 hr); H2 -receptor antagonist ineffective in massive GI bleeding (should not be used unless patient has allergy
to PPI); clearing blood—erythromycin has role when preparing patient for endoscopy (minimizes need for second look);
formerly, patients lavaged with 4 to 10 L of saline (risk for aspiration and hypothermia); administer erythromycin 250 mg
IV; can also clear blood by moving patient (normally, patients evaluated for esophagoduodenoscopy [EGD] in left lateral
position); switching patient to his or her back or to right (gravity switches fluid level), allows better evaluation of areas of
stomach; picking right scope—for patient who returns with upper GI bleeding from endoscopic retrograde cholangiopancreatography
(ERCP) in past 2 days, use side-view scope to obtain better view of periampullary region; for those presenting
with large amount of blood that cannot be removed, therapeutic gastroscope used; double-lumen scope allows
physician to put instrumentation down one side while still aspirating and irrigating
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| Tools: thermal—contact (touches tissues) or noncontact; coaptive coagulation not only delivers thermal energy but also
causes vascular constriction and occlusion (by tamponade); also gets rid of heat sink; probes come in different sizes; need
to be more careful in duodenum and cecum (thin-walled organs) and may have to use noncontact or nonthermal energy or
delivery system; how hard to push or to deliver energy depends on what is being treated; if peptic ulcer, can deliver more
energy (push firmly, set joules higher, and deliver energy at multiple occurrences); if angioma, be more gentle, reduce
joules, and make only 1 to 2 attempts at coagulation; noncontact thermal tools—eg, argon; resembles paint brush; delivers
energy at superficial level via argon gas; has lower depth of penetration; argon used more frequently in colon; combination
therapy (injection therapy with thermal energy) most effective way to minimize rebleeding; nonthermal
methods—injection of sclerosants; rubber bands; clips; endoloops; injection therapy simple, low-tech, and readily available;
epinephrine 1:10,000 ratio commonly used with or without sclerosing agent; alcohol also used; gold probe has injection
needle with bipolar circumactive (BICAP) probe; if source of bleeding not identified and removed, higher chance
of rebleeding; large-volume injections of epinephrine more effective than small volumes; use caution if giving 45 mL of
epinephrine and whole amount absorbed (patient becomes tachycardic and hypertensive, especially if patient older and
has coronary disease); if more volume needed, give more diluted epinephrine; with alcohol, cannot increase to more than
≈2 mL, and benefit of volume effect lost; probe size—use larger probe with therapeutic scope and larger channel (minimizes
risk because not necessary to coagulate as much; reduces risk for perforation and, in several series, reduces hospital
stay); clips—commonly used; somewhat costly; not as effective in bleeding; disadvantage diameter opening not wide
and not enough depth of grasp
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| Rebleeding: those with active bleeding at time of endoscopic evaluation, those with large nonbleeding visible vessel, and
those with clot have highest risk for rebleeding; those with stigmata of bleeding inside ulcer and those with clean base
have much lower risk (comprises 75% of sources of bleeding that can be identified); repeat endoscopy—no reduction in
risk for rebleeding; consider in those with high risk for rebleeding and in those who had suboptimal therapy at first endoscopy;
decreases need for surgery; by stopping bleeding before surgery, less blood lost; indications for surgery—failed
endoscopic management; returning to hospital with hemodynamic instability
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| Algorithm for acute ulcer bleeding: high-risk patients—include those with comorbidities, older age, hypertension, and
massive transfusion requirements; also those who are coagulopathic; require rapid endoscopic evaluation; after endoscopy,
evaluate risk for rebleeding; if low risk with no visible vessels, active bleeding, or deep ulcerations, discharge
home with oral PPI (look for Helicobacter pylori in these patients); if high risk, place in ICU with IV PPIs and consider
second-look endoscopy; scope immediately in cases of hemodynamic instability or difficulty maintaining hemodynamic
stability and active bleeding
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| Gastric antral arteriovenous malformations (AVMs): also known as vascular ectasia; patients usually have underlying
disease, eg, cirrhosis, portal gastropathy; consider noncontact endoscopic treatment; usually require 3 to 4 treatments;
treat with argon plasma coagulation (APC); somewhat difficult to treat; isolated angiodysplasias superficial; be careful
in providing extensive level of joules or multiple power agents if in cecum or duodenum (reduce energy provided); difficult
to prove as source of bleeding; high risk for multicentricity; Dieulafoy’s lesion—isolated submucosal vessel
found anywhere in GI tract (predominantly in stomach); managed with combination of thermal and nonthermal energy;
rarely requires surgery, but if necessary, “tattoo” lesion (difficult to locate in operating room); high risk for rebleeding;
Mallory-Weiss tears—usually accompany history of active vomiting episode; do not usually require surgery; usually
require blood transfusion (2-4 U); exercise caution if providing thermal energy (loss of mucosa); instead, speaker uses
injection sclerotherapy or clipping
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| Doppler ultrasonography (US): not like endoscopic US; portable; helps identify whether active vessel present at base of
ulceration; differentiates arterial- from venous-type blood flow; differentiates varices from nonvarices; may predict risk
for rebleeding; patient with continued positive Doppler US has 3 times higher risk for rebleeding over next 3 days
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| ENDOSCOPIC MANAGEMENT OF GI BLEEDING —David A. Johnson, MD, Professor of Medicine and Chief of Gastroenterology,
Eastern Virginia Medical School, Norfolk, VA
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| Case: man, 62 yr of age, presents in ED with hematemesis (“dark coffee grounds”) and frequent melena (4 episodes in last
6 hr); on nonsteroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis and on aspirin; physical examination performed;
patient pale, diaphoretic, and hypotensive, with blackish and reddish stools on rectal examination; actively
bleeding
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| Endoscopy: triage tool; 95% accurate in determining cause and predicting outcome of rebleeding; allows for change in natural
history, bed direction, and management flow and avoids issues of constant monitoring in relation to possible transfusion;
can perform early endoscopy and discharge patient from ED if lesion has low risk for rebleeding; scoring tools
available to predict rebleeding; literature to support use of Doppler US as stratification tool; erythromycin—motilin agonist;
stimulates migrating motor complex; 2 randomized controlled trials (RCTs) in which patient receiving 250 mg of
erythromycin before endoscopy had better clearance of stomach; simple
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| Injection therapies: epinephrine—has tamponade and vasoconstrictive effects; reduces bleeding by 40% to 50% in trials;
larger volume better (target ≈10 mL); sclerosants—work as tissue desiccants that promote thrombosis; data show efficacy
inferior to epinephrine, but combination of these 2 agents works better than either one alone; shorten hospital stay
and improve outcome; sealants and glue—used with variable results; cyanoacrylate—used primarily for varices (gastrocardial
varices); limited data for use in peptic bleeding; risks include embolization; state of art—injection therapy
safe; epinephrine has fewest complications but should not be administered as sole agent
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| Thermal therapies: noncontact-type used in past; laser—not practical for GI bleeding and nontransportable; comparable
to injection therapy; technical strengths limit use; APC—can be taken to bedside; simple and easy to perform; develops
tissue damage and coagulation effect with superficial injury; prospective studies show improvement in hemostasis and
particularly more for second technique once epinephrine injected; in RCTs, comparable to heater probe with epinephrine;
speaker uses most frequently in vascular ectasia that creates bleeding; bipolar coagulation—hemostasis through coaptation,
hermetically sealing vessel by administration of current; easy to perform; injector with gold probe comparable, with
ability to inject and deliver BICAP; reduces bleeding, compared to normal saline injection alone; easy to perform in combination
with epinephrine; caveat—do not use BICAP after alcohol or sclerosant; heater probe—comparable to BICAP
device
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| Mechanical techniques: hemoclip—safe and effective; question whether cost justified; lower bleeding rates than injection
alone; additional benefit of injection unclear; technical predictors of failure—in administration, en face approach necessary
(sometimes precluded by tangential angle); particularly in antral (posterior wall, greater curvature), gastric body
(lesser curvature), and duodenal (posterior wall) lesions; helpful to have previous epinephrine injection; need space for
deployment; advances include repositioning clips and multiple clips; band ligation—used in peptic bleeding; not used
routinely by speaker; problematic; reasonable in Dieulafoy’s lesion
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| Dual therapy vs monotherapy: meta-analysis of 20 studies (nearly 2500 patients) showed risk reduction in recurrent
bleeding with monotherapy but less than risk reduction with dual therapy
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| Adherent clots: role of interventional therapy—early data showed no benefit; meta-analysis suggests benefit if visible
vessel present; adherence of clot depends on clot irrigation technique; optimal technique for removal unclear; value of
clot removal clear; if high-risk stigmata found, changes natural history; vigorously lavage and remove clot with device if
possible; treat lesion if appropriate
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| Second-look endoscopy: studies show not beneficial in outcome; indicated if rebleeding or initial procedure unsuccessful
or partial; endoscopy should still be done, even if patient on active anticoagulation
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| Role of medical therapy: in 5 meta-analyses, no benefit in risk reduction shown, but one study from Hong Kong showed
risk reduction for rebleeding; omeprazole given IV followed by continuous infusion for 72 hr; high-dose oral omeprazole
also effective
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| Take-home message: addition of second intervention to epinephrine necessary (standard of care); injection not superior to
thermal or mechanical monotherapy
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| Management of case: patient given erythromycin, then combination therapy used (epinephrine injection, then clip applied);
started on IV PPI, then switched to oral PPI; patient discharged within 72 hr
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| PHARMACOTHERAPY IN GI BLEEDING: WHAT’S THE ROLE, WHAT ARE THE DATA ?—M. Brian Fennerty,
MD, Professor of Medicine, Oregon Health Sciences University, Portland, OR
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| Introduction: meta-analysis—2000 patients; 14 trials; risk for rebleeding reduced by one-half in patients with ulcer bleeding
on somatostatin or octreotide; tranexamic acid—meta-analysis (1989); 1200 patients; 6 trials; reduced rebleeding rates by
70% to 80%, surgery by 60% to 70%, and mortality rates by >50%
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| H2 blockers and PPIs: correlation between gastric pH and clot stabilization and platelet aggregation; greater pH (closer to
neutral) and greater clot stability and platelet function; to affect clot function and platelet aggregation, need to maintain
pH at 7 to have sufficient time for cross-linking of collagen to occur; medical achlorhydria trial—compared standard
therapy in 1980s (intermittent infusion of cimetidine 300 mg q6h) to continuous-infusion IV cimetidine and calcium carbonate
(Maalox) therapeutic concentrate drip down nasogastric tube; rebleeding rates 11% for control group and 17% for
others (not statistically significant); results showed no difference in outcome (enrollment of wrong patient population [almost
all patients had clean-based ulcers or just flat spots, with rebleeding rates near zero]); study—patients with ulcer
disease given IV bolus of omeprazole, followed by continuous infusion of omeprazole or continuous infusion of ranitidine;
showed that PPIs could raise and maintain pH with continuous infusion; other studies show that not necessary to
give continuous infusion to have same effect (as long as given IV >2 times daily); trial—looked at oral PPI therapy for
bleeding peptic ulcers; Kashmir region of India; unequivocally showed that PPIs, as only intervention for patient with
bleeding ulcer, had marked impact on surgery and rebleeding rates (also on death and transfusion); similar trial showed
significant impact on surgery, rebleeding, and transfusion with oral PPIs and therapeutic endoscopy; trial—Taiwan;
omeprazole vs cimetidine; patients followed for 3 days, then given oral PPI or H2 blocker and sent home for 2 mo;
showed PPI significantly better than H2 blocker; trial—patients randomized to IV therapy with omeprazole or placebo
after endoscopic attention given to ulcer; effect on surgery, bleeding, and death improved; trial—compared endoscopic
treatment with IV PPI to IV PPI alone; used epinephrine with heater probe for therapy through endoscope and IV omeprazole
in standard dose; showed combination superior to IV PPI alone; some data to show that benefit derived from simply
using PPI after endoscopic therapy for ulcer (not from IV use of PPI); varied studies available; magnitude of effect of
PPI (IV or oral) on ulcer rebleeding ranges from 4% to 11%; single trial showed rebleeding rate of 0% after IV PPI combined
with endoscopic therapy (never replicated); trial—first North American (Canada) study looking at impact of IV
PPI on ulcer bleeding; compared IV pantoprazole with IV ranitidine; rebleeding, surgery, and death rates unchanged in
each arm; predominance of data show that PPIs effective and standard of care; most of data with IV PPIs given as continuous
infusion; unknown—whether oral PPI as effective as IV PPI with and without endoscopic therapy; optimal dose and
frequency of oral PPI; impact of newer-generation acid pump blockers (eg, immediate-release omeprazole)
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Suggested Reading
Cheng CL et al: Endoscopic management of Dieulafoy lesions in acute nonvariceal upper gastrointestinal bleeding. Dig
Dis Sci 49:1139, 2004; Church NI et al: A randomized trial comparing heater probe plus thrombin with heater probe plus
placebo for bleeding peptic ulcer. Gastroenterology 125:396, 2003; Coffin B et al: Injection therapies for nonvariceal
bleeding disorders of the GI tract. Gastrointest Endosc 66:343, 2007; Jensen DM et al: The cost-effectiveness and budget
impact of intravenous versus oral proton pump inhibitors in peptic ulcer hemorrhage. Clin Gastroenterol Hepatol 4:988,
2006; Jensen DM: Treatment of patients at high risk for recurrent bleeding from a peptic ulcer. Ann Intern Med 139:294,
2003; Kahi CJ et al: Endoscopic therapy versus medical therapy for bleeding peptic ulcer with adherent clot: a meta-
analysis. Gastroenterology 129:855, 2005; Kubba AK et al: Update in the pharmacological management of peptic ulcer
haemorrhage. Scand J Gastroenterol 36:337, 2001; Laine L: Systematic review of endoscopic therapy for ulcers with
clots: Can a meta-analysis be misleading? Gastroenterology 129:2127; author reply 2127, 2005; Marmo R et al: Dual
therapy versus monotherapy in the endoscopic treatment of high-risk bleeding ulcers: a meta-analysis of controlled trials.
Am J Gastroenterol 102:279, 2007; Selby NM et al: Acid suppression in peptic ulcer haemorrhage: a 'meta-analysis'. Aliment
Pharmacol Ther 14:1119, 2000; Shin WG et al: Obscure gastrointestinal bleeding. Gut 55:1560, 1585, 2006.
Educational Objectives
| The goal of this program is to improve the management of gastrointestinal (GI) bleeding. After hearing and assimilating this
program, the clinician will be better able to:
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 | 1. Utilize the appropriate tools to manage upper GI bleeding.
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| 2. Determine those who are at high risk for rebleeding.
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| 3. Recognize gastric antral arteriovenous malformations as causes for GI bleeding.
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| 4. Describe the therapies available to manage GI bleeding.
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| 5. Recognize the importance of proton pump inhibitors as the standard of care in the management of GI bleeding.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and planning committee
members to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest.
Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a
proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Marks receives laboratory
support and speaker honoraria from Boston Scientific and is a consultant for Tyco. Dr. Fennerty is a consultant for AstraZeneca,
TAP Pharmaceuticals, and Santarus. Dr. Johnson and the planning committee reported nothing to disclose.
Acknowledgments
Dr. Marks was recorded at the 2nd Annual Surgery Update Course, held November 10-11, 2006, in Cleveland, OH, and
sponsored by the Case Western Reserve University School of Medicine, Department of Surgery. Dr. Johnson was recorded
at the 32nd Annual Texas Program, held September 14-16, 2007, in Grapevine, TX, and sponsored by the Texas Society for
Gastroenterology and Endoscopy, the American College of Gastroenterology, and the SGNA Texas Regional Societies. Dr.
Fennerty was recorded at Frontiers in Endoscopy, held December 13-16, 2006, in New York, NY, and sponsored by the
New York Society for Gastrointestinal Endoscopy. The Audio-Digest Foundation thanks the speakers and the sponsors for
their cooperation in the production of this program.
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