UPPER GASTROINTESTINAL BLEEDING. Causes of Esophago-Gastro- Duodenal Bleeding Varices Mallory Weiss NSAID’s/ Aspirin Neoplasm Acute Gastritis Arterio-Venous.

UPPER GASTROINTESTINAL BLEEDING

Causes of Esophago-Gastro-Duodenal Bleeding

Varices

Mallory Weiss

NSAID’s/Aspirin

Neoplasm

Acute Gastritis

Arterio-VenousMalformation

Duodenal Ulcer

Gastric Ulcer

Esophagitis

Upper Gastrointestinal Bleeding

Upper Gastrointestinal Bleeding

Upper Gastrointestinal Bleeding

Severe UGIH is a common

and

serious medico-surgical problem

Upper Gastrointestinal Bleeding

Despite a decreased incidence of ulcer

disease and improvements in the

management of acute upper GI bleeding,

mortality remains at + 6-7 % in most series

in the literature for the past 30 years.

Upper Gastrointestinal Bleeding

Endoscopic hemostatic therapy

has been demonstrated to be the

mainstay of management.

Upper Gastrointestinal Bleeding

At intragastric pH < 7, coagulation is

deficient due to ineffective function

of clotting factors and platelets

Upper Gastrointestinal Bleeding

Maintenance of a high intragastric

pH > 6 during management of upper

G I Bleeding is warranted.

IV PPI’s are able to maintain gastric

pH > 6 for 24 hours a day.

Upper Gastrointestinal Bleeding

Recent clinical trial data support the

use of PPI’s to decrease the rate of

re-bleeding and the need for surgery.

Epidemiology of upper GI Bleeding

100 cases/100,000 adults/year

50-60% of cases are peptic ulcer disease

150,000 hospital admissions/y (U.S. 1985)

80% of cases of bleeding cease spontaneously

6-7% mortality rate

Upper GI bleeding

Pathophysiology

Risk factors for ulcers and bleeding

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 as 75 mg day ASA

Corticosteroid + 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

NSAID Induced Ulcers

Main Risk Factors:

Older age > 75 years

Active R.A.

Concomitant use of corticosteroids

History of peptic ulcer disease, GI bleeding or heart disease.

Prognostic Factors

Clinical:

Haemodynamic instability

Fresh red blood in the emesis

Haematochezia

Increasing number of units transfused

Prognostic Factors

Age > 60 years

Concurrent illness - Cardiovascular, pulmonary and Diabetes Mellitus

Onset while hospitalised for other reasons

Recurrent bleeding

Prognostic Factors

Urgent Endoscopy:

Patients with coffee-ground vomiting with melena

Haematemesis with or without melena

Prognostic factors: endoscopic

80%

60%

40%

20%

0%Clean base Flat spot Adherent

clot

% o

f p

atie

nts

reb

leed

ing

Laine & Peterson; 1994

Incidence of rebleeding by appearance of ulcer at endoscopy

Nonbleeding visible vessel

Active bleeding

5 10

22

43

55

Outcome of Acute G I Bleeding

Influence of Diagnosis on Outcome

Vascular Anatomy

Vascular Anatomy - Relationship to Therapy

Role of Endoscopy

Forrest Classification

Endoscopic Observation Rebleeding Chance %

Ia Spurting Arterial bleed 80-90

Ib Oozing bleed 10-30

IIa Non-bleeding visible vessel 50-60

IIb Adherent clot 20-35

IIc Black hematin ulcer base 0-8

III Clean ulcer base 0-12

Endoscopic intervention is only required

in Forrest Ia, Ib, IIa and probably IIb

at first to stop the active bleeding (Ia, Ib)

and prevent subsequent rebleeding.

In Forrest IIb (probably), but surely IIc

and III, the risk of rebleeding is very low

and does not warrant active endoscopic

hemostatic techniques.

Stigmata of Recent Haemorrhage - Prevalence

Nature of the visible vessel

Overview of management

Initial management

Endoscopic therapy

Surgical therapy

Pharmacological therapy

Initial Management

Assess haemodynamic instability

Resuscitation

Haemogram and coagulation studies

Nasogastric tube (in/out)

Monitoring of vital signs and urine output

Endoscopic therapy

Perform early (ideally within 24 h)

Indications for haemostatic therapy1

1. +/- Adherent clot 2. Nonbleeding visible vessel 3. Active bleeding (oozing, spurting)

Heater probe, bipolar electrocoagulation or injection therapy

Decreases in rebleeding, surgery and mortality2,3

1. Laine & Peterson; 19942. Cook et al; 19923. Sacks et al; 1990

Effect of Therapy on re-bleeding rates (Visible Vessel)

Effect of Therapy on re-bleeding rates (Active Bleeding)

In a comparative study (AJG 2001) between adrenaline injection alone

and adrenaline followed by hemoclips

in Forrest Type I or II patients

Control of bleeding achieved in 83,3% of patients in the injection - only group and 95,6% in the combination group (NSS)

In sub-group Forrest Ib patients, rebleeding was 31% in the

injection - only group and 0% for the combination group (p< 0,05)

Re-bleeding rate in adrenaline - only group is 17% compared to 4,42% in the combination group - clinically meaningful but NSS.

Endoscopic therapy may not be

possible in up to 12% of bleeding

duodenal ulcers and at least 1% of

bleeding gastric ulcers because of

inaccessibility of the lesion or massive

hemorrhage.

Patients who do not have active

bleeding, non-bleeding visible vessels,

or adherent clots are low risk for further

bleeding.

Bleeding from a P.U. recurs after initial

endoscopic hemostasis in 15-20% of

patients.

Endoscopic re-treatment reduces the

need for surgery without increasing the

risk of death and is associated with

fewer complications than surgery

Hypotension and ulcer size of at least 2cm

are independent factors predictive of the

failure of endoscopic re-treatment.

Patients with larger ulcers and therefore

heavier bleeding, surgery may be a better

choice than endoscopic re-treatment.

Salvage surgery for recurrent bleeding

is associated with a mortality rate

ranging from 15-25%.

Surgical therapy

Endoscopic management failure

Other extenuating circumstances

Patient survival improved by optimal timing

Individualized by clinical context, endoscopic and surgical expertise

- lowers splanchnic blood pressure

- induces vasoconstriction

- high rate of complications

Pharmacological Therapy

Vasopressin

- Lower toxicity

- additional effects of decreasing gastric acid secretion and increasing duodenal bicarbonate secretion

- decreased risk of re-bleeding compared to H2RAs

Pharmacological Therapy

Somatostatin and Octreotide

- appears to decrease mortality

- increased risk of thrombo-embolic events

Pharmacological Therapy

Tranexamic acid - Antifibrinolytic agent

Acid suppressing agents

- H2 Receptor Antagonists

- Proton Pump Inhibitors

Pharmacologic Therapy

Aggressive acid suppression with PPI’s

reduce the rate of recurrent bleeding, the

need for transfusions, and the need for surgery.

They represent an important adjunct to

endoscopic therapy.

Pharmacologic Therapy

Role of acid in haemostasis

Impairs clot formation

– Impairs platelet aggregation and causes

disaggregation

Accelerates clot lysis

Predominantly acid-stimulated pepsin

May impair integrity of mucus/bicarbonate barrier

pH = 7.4

Ag

gre

gat

ion

(%

)Effect of plasma pH on platelet aggregation

Green et al; 1978

Time (minutes)

0

20

40

60

80

1000 1 2 3 4 5

pH = 5.9

pH = 6.8

A

ADP

Effect of PPI on gastric pH

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

No reported tolerance

Continuous infusion (CI) superior to intermittent bolusadministration

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

Role of Omeprazole in the treatment of Upper G I Bleeding

Omeprazole in the Upper GI Bleeding Patients with Stigmata of recent haemorrhage

Omeprazole therapy in the treatment of upper GI bleeding from specific lesions

Prevention of Recurrent Upper GI Bleeding

Eradication of H pylori Effect on Re-bleeding (D.U.)

Role of PPI for upper GI bleeding: summary (1)

H2RAs

Unlikely to provide necessary pH increase

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

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 PPI therapy

Role of PPI for upper GI bleeding: summary (2)

Stress Bleeding prophylaxis - Indications

Stress Prophylaxis - Treatment

MethodTranscatheter embolization - gel foam or pharmacotherapy - vasopressin

Role of Angiography

Goal

Stop the bleeding

Requirements

Failure of endoscopic therapy favourable anatomical location

Oesophageal varices cause + 10% of

cases of acute upper GI bleeding

admitted to hospitals

Variceal Haemorrhage

Mortality rate 30-50%

Gastro-oesophageal varices are present

in + 50% of cirrhotic patients. Their

presence correlates with severity of liver

disease

Variceal Haemorrhage

Bleeding from oesophageal varices

ceases spontaneously in up to 40% of

patients

Control of hemorrhage (24 hour

bleeding free period within first

48 hours after therapy)

Treatment of Acute Variceal Hemorrhage

Prevention of early recurrence

High rate of major complications

Pharmacotherapy

Vasoactive therapy - Vasopressin

Conflicting results with Terlipressin

and Nitroglycerin

Native Somatostatin

Reduces splanchnic blood flow and

azygos blood flow

Use is restricted due to its short half

life

(1-2 min)

Pharmacotherapy

Is as effective as endoscopic

sclerotherapy and is a safe treatment for acute variceal bleeding

Pharmacotherapy

Synthetic somatostatin analogue - Octreotide

Half life 1-2 hours

More effective than placebo, vasopressin and balloon tamponade

Non selective ß-adrenergic blockers - proprandolol, nadolol or timolol

Pharmacotherapy

They decrease portal venous inflow by two mechanisms

- decreasing cardiac output (ß1 blockade)

- splanchnic vasoconstriction (ß2 blockade and unopposed alpha adrenergic activity)

Antibiotic prophilaxis is mandatory

Pharmacotherapy

- Reduces rate of bacterial infections- Increases survival

Avoid intravascular over expansion

Blood replacement to target Hematocrit of

25-30%

Octreotide as adjunct to endoscopic

therapy appears to be the most

promising approach in the treatment of

acute variceal hemorrhage

Endoscopic View of Oesophageal Varices

Oesophageal Varices - Sclerotherapy

Oesophageal Varices - Banding

Shunt surgery (distal spleno-renal)

in well compensated liver disease

(Child A) or TIPS are of proven

clinical efficacy as salvage therapy

for patients not responding to

endoscopic or pharmacologic therapy

Shunt Therapy

prevents rebleeding

Shunt Surgery

increases risk of portosystemic encephalopathy

no effect on survival

reduces rebleeding

encephalopathy no effect on survival

shunt dysfunction

T I P S