UGI Bleeding

Epidemiology of Upper GI Bleeding

• Bleeding from a source above the ligament of Treitz

• 1 case/1,000 adults/year

• 50% of cases are peptic ulcer disease (25% rebleed)

• 40-80% of cases of bleeding cease spontaneously

• 10% mortality rate

Prognostic Factors

• Hemodynamic instability

• Hematochezia from upper GI source

• Increasing number of units transfused

• Age > 60 years

• Concurrent illness (cardiac, respiratory, renal, neoplastic, CNS)

• Onset while hospitalized for other reason• Coagulopathy

Etiology of UGI Bleeding

Non GI• Hemopytsis, nose bleed

Esophageal• Esophagitis, ulcer, varices, malignancy, MW tear

Gastric• Gastritis, ulcer, varices, malignancy, AVM

Duodenal• Duodenitis, ulcer, varices, malignacy (rare),

AVM, aortoenteric fistula

Etiology Incidence

1. PUD 50%

2. Esophagitis 15%

3. Gastritis 10%

4. Varices 10%

5. Duodenitis 5%

6. MW tear 3% (much more common in young)

7. Esophageal ulcer 3%

8. Carcinoma 3%

Presentation

• Melena or hematochezia 70% (charting, iron pepto)

• Hematemesis or coffee ground emesis 30% (charting, testing)

• Syncope 14%, presyncope 40%• Heartburn 40%, epigastric pain 20%• Dysphagia 10%• Wt. loss 12%

Important History

• Evidence of complications CP/SOB/presyncope• Appearance, frequency and amount of vomit/BM

(elderly unreliable)• Duration of symptoms• Use of NSAID/ASA/corticosteroids• Previous history of GI bleeding• Co-morbidities = cardiac, respiratory, neoplastic,

CNS

Physical Exam

• ABC’s• Vitals• Orthostatic bp (scoping)• Rectal exam (what does –ve OB really mean)

Initial Management• ABC’s• Npo• Head down, raise legs• 2 IV’s• CBC• Urea/Cr (? upper vs lower bleeding, ? reliable)• G&T• LFTs• Coagulation status• ECG/cardiac enzymes• NG?

Prognostic Factors: Endoscopic

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Clean base Flat spot Adherent clot Nonbleedingvisible vessel

Activebleeding

Incidence of Rebleeding by Appearance of Ulcer at Endoscopy

Laine, Peterson, N Engl J Med 1994.

Clot on Vessel - Gastric Ulcer

Overview of Management

• Initial management

• Endoscopic therapy

• Surgical therapy

• Pharmacologic therapy

Endoscopic Therapy

• Perform early (ideally within 24 h)

• Indications for haemostatic therapy:• (1) +/-Adherent clot, (2) Nonbleeding visible

vessel, (3) Active bleeding (oozing, spurting) (Laine, Peterson. 1994)

• Heater probe, bipolar electrocoagulation or injection therapy

• Decreases in rebleeding, surgery and mortality (Cook, et al. 1992, Sacks, et al. 1990)

Surgical Therapy

• Endoscopic management failure

• Other extenuating circumstances

• Patient survival improved by optimal timing

• Individualized by clinical context, endoscopic and surgical expertise

Surgical Therapy

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36%

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18%

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Surgery Complications Mortality

Endoscopic retreatment group (n=48) Surgery group (n=44)

N/A

P=0.03

P=0.37

Outcomes in 92 patients with rebleeding after endoscopic therapy: endoscopic retreatment vs.

surgery.

Lau, et al. NEJM 1999. N/A=not applicable

Pharmacologic Therapy

• Splanchnic blood pressure modifiers• vasopressin, somatostatin, octreotide

• Anti-fibrinolytic agents• tranexamic acid

• Acid suppressing agents• H2-receptor antagonists (H2RAs),

proton pump inhibitors (PPIs)

Somatostatin/Octreotide

• Effects:• Lowers splanchnic blood pressure• Decreases gastric acid secretion• Increases duodenal bicarbonate secretion

• Meta-analysis: (Imperiale, Birgisson, 1997)

• 14 trials (n=1,829); SOM (12 trials), OCT (2 trials)• 0.53 risk of rebleeding vs. H2RAs• RR=0.73 among investigator-blinded trials• Studies did not control for confounders, i.e.,

endoscopic therapy

Acid Suppressing Agents

• H2-receptor antagonists (H2RAs)• Cimetidine, ranitidine, famotidine,

nizatidine

• Proton pump inhibitors (PPIs)• Pantoprazole, omeprazole (oral, IV)• Esomeprazole (Nexium) (oral)• Lansoprazole (oral)

Role of Acid in Hemostasis

• Impairs clot formation • Impairs platelet aggregation & causes

disaggregation

• Accelerates clot lysis • Predominantly acid-stimulated pepsin

• May impair integrity of mucus/bicarbonate barrier

Effect of PPI on Gastric pH

• Increase intragastric pH• pH>6.0 for 84->99% of day

• Continuous infusion (CI) superior to intermittent bolus administration

• Clinical improvements in rebleeding and/or surgery with: Bolus 80 mg + CI 8 mg/h

Role of PPI For UGI Bleeding:Summary of Clinical Trials

• 10 RCTs• PPI (n=1,150); controls (n= 1,142)

• Minimal benefit with intermittent bolus

• Clinical benefits with bolus plus continuous infusion (CI)• Decreased need for surgery and/or rebleeding• Dose: Bolus 80 mg + CI 8 mg/h x 3 d

Role of PPI For Upper GI Bleeding:Summary

• H2RAs • Unlikely to provide necessary pH increases

• Tolerance a problem• Minimal benefit in clinical trials

• PPIs can provide profound acid suppression• pH>6.0 over 24-hours• Suggested benefits on rebleeding and/or need

for surgery• Mortality benefits not yet demonstrated

Role of PPI For Upper GI Bleeding:Summary

• Reasonable to consider initiating as soon as possible following presentation to hospital

• Administer as bolus + continuous infusion (CI)• IV bolus 80 mg + CI 8 mg/h x 3 d

• Continue therapy, probably with an oral PPI

• Likely most beneficial for patients with high risk, non-actively bleeding lesions

• Further trials needed to determine optimal patient group for acute IV PPI therapy

Peptic Ulcer Disease

Causes:• Infectious: H.P., Herpes, CMV• Drugs: NSAIDS, corticosteroids• Neoplastic• ICU Stress

Types:• DU = pain between meals• GU = pain with meals, epigastric

Risk Factor

H. pylori - 70-90% in non-bleeding duodenal

ulcers

- Lower in bleeding ulcers and gastric

ulcers

NSAIDs/ASA(dose dependent)

- Increased risk of ulcers and bleeding

with doses as low 75 mg day ASA

Corticosteroids+ NSAIDs

- Little increased risk when used alone- With NSAIDs increased risk:

- Ulcer complications – 2 X- GI bleeding – 10 X

Oral anti-coagulants+/- NSAIDs

- Increased risk of bleeding vs. controls:- Alone – 3.3- With NSAIDs – 12.7

Risk Factors for Ulcers and Bleeding

Peptic Ulcer Disease – Helicobacter Pylori

• Most common chronic bacterial infection in man• 15% of infected go on to PUD• Dx via C13/C14 breath testing, histology, serology,

urease testing (5-15% false negative)– false negative if ABO or acid suppression within the

last week (except serology)

• Serology $30 (not for eradication)• Breath Testing 13C non-radioactive urea

metabolized to CO2 exhaled and quantified

Peptic Ulcer Disease – When to Test for H.P.

• GU = test for H.P. as other causes of GU are common, especially NSAID induced ulcers, maliganancy (repeat endoscopy)

• DU = if not on NSAID may treat empirically for H.P.

Helicobacter Pylori Eradication

• Proven to decrease ulcer recurrence/bleeding• Tx if any history of upper GI bleeding and H.P.

positive

Treatment Options:• PCA= PPI + Clarithomycin 500mg bid + Amoxil

1g bid for 7 days• PCM = PPI + Clarithoromycin 500mg bid +

Metronidazole 500 mg bid X 7 days (resistance)

H.P. Eradication

• Antibiotics are very effective • Test for eradication only in complicated ulcer

disease eg. bleeding, pyloric outlet obstruction, recurrent ulceration or persistent symptoms

• Most cost effective method = breath testing – 1/12 after antibiotics are complete– 7/7 after stopping acid suppression

NSAID And Upper GI Ulceration

• 2-4% annual risk of PUD related complication on NSAID (bleeding, outlet obstruction, symptomatic ulcer)

• Lowest possible dose of NSAID/ASA (2-4X risk even if <325 mg ASA daily)

• Prophylaxis if:– Previous PUD or GI bleed – NSAID + corticosteroids– >65 (75 in Ontario guidelines) – serious comorbidity

NSAIDS & UGI Bleeding

• Classic NSAID inhibit COX-1 and COX-2• Inhibition of COX 1 results in decreased gastric

PG and hence poor protective barrier in the GI tract

• COX-2 expressed predominantly in actively inflammed tissues, therefore less damage to normal GI tract

• COX-2 ulcer risk approx to that of classic NSAID + PPI

COX-2 Inhibitors & UGI Ulceration

46

26

0

5

10

15

20

25

30

% of patients with GI

ulceration at 12 weeks

Drug

PlaceboCelecoxibNaproxen

• 1149 pt. with R.A. endoscopy pre and post 12 weeks therapy for GI ulceration

• Compared celecoxib (2x max. dose) vs. naproxen (max. dose) vs. placebo

• No difference ulceration between placebo and celecoxib vs. p<0.001 difference between celecoxib and naproxen

• Near identical study with Vioxx (rofecoxib)

NSAIDS and UGI Bleeding Prophylaxis

Options:• Misoprostol 200mg qid + standard NSAID

– Side effects diarrhea, cramps– $38/month, 4% S/E

• PPI + standard NSAID– More effective than Misoprostol– $53/month (Pantoprazole)

• Cox –2 inhibitor ($40-75/month)– ? Add PPI

NSAIDS, H.P. And UGIB Prophylaxis

• In high risk patients (previous PUD or ongoing dyspepsia), test and treat for H.P. prior to NSAID initiation decreases risk UGI to that of PPI or celebrex

• How to test• Time consideration of breath testing• Most bleeds in first month

• Previous studies show no benefit for primary prophylaxis with H.P. eradication if already on an NSAID

Esophageal Variceal Bleeding

• BE SUPICIOUS, if patient is cirrhotic/heavy drinker think varices first

• 30-50% mortality without early intervention• Causes of death are classically aspiration, sepsis,

renal failure or encephalopathy • Treatment options:

- Medical - endoscopic- Tamponade - TIPS

- Surgical

Esophageal Variceal Bleeding

• Medical = octreotide (72 hours) or somatostatin forget vasopressin

• Endoscopic = ligation (banding), sclerotherapy

Esophageal Varices

• Tamponade = Blakemore tube

                                   

                                     

Esophageal VaricesTIPS = transjugular intrahepatic portosystemic

shunts or Surgical Shunts = desperate measures

TIPS

TIPS

TIPS