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
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
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
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.
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
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.
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
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 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)
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
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