UPPER GASTROINTESTINAL BLEEDING

Causes of Esophago-Gastro-Duodenal Bleeding Varices Mallory Weiss Esophagitis Gastric Ulcer NSAID’s/ Aspirin Neoplasm Acute Gastritis Duodenal Ulcer Arterio-Venous Malformation

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 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 Incidence of rebleeding by appearance of ulcer at endoscopy 80% 60% 40% 20% 0% % of patients rebleeding 55 43 22 10 5 Clean base Flat spot Adherent clot Nonbleeding visible vessel Active bleeding Laine & Peterson; 1994

Outcome of Acute G I Bleeding

Influence of Diagnosis on Outcome

Vascular Anatomy

Relationship to Therapy Vascular Anatomy - Relationship to Therapy

Role of Endoscopy

Forrest Classification Endoscopic Observation Rebleeding Chance %

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 Resuscitation Haemogram and coagulation studies 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; 1994 2. Cook et al; 1992 3. 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, 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

Pharmacological Therapy Vasopressin - lowers splanchnic blood pressure - induces vasoconstriction - high rate of complications

Pharmacological Therapy - Lower toxicity - additional effects of decreasing gastric acid secretion and increasing duodenal bicarbonate secretion - decreased risk of re-bleeding compared to H2RAs Somatostatin and Octreotide

Pharmacological Therapy - appears to decrease mortality - increased risk of thrombo-embolic events Tranexamic acid - Antifibrinolytic agent

Pharmacologic Therapy 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.

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

Effect of plasma pH on platelet aggregation  20 40 60 80 100 pH = 5.9  ADP pH = 6.8 pH = 7.4 Aggregation (%) 0 1 2 3 4 5 Time (minutes) Green et al; 1978

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 bolus administration 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

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

Stress Bleeding prophylaxis - Indications

Stress Prophylaxis - Treatment

Role of Angiography Goal Requirements Failure of endoscopic therapy Stop the bleeding Requirements Failure of endoscopic therapy favourable anatomical location Method Transcatheter embolization - gel foam or pharmacotherapy - vasopressin

Variceal Haemorrhage Oesophageal varices cause + 10% of cases of acute upper GI bleeding admitted to hospitals Mortality rate 30-50%

Variceal Haemorrhage Gastro-oesophageal varices are present in + 50% of cirrhotic patients. Their presence correlates with severity of liver disease Bleeding from oesophageal varices ceases spontaneously in up to 40% of patients

Treatment of Acute Variceal Hemorrhage Control of hemorrhage (24 hour bleeding free period within first 48 hours after therapy) Prevention of early recurrence

Pharmacotherapy Vasoactive therapy - Vasopressin High rate of major complications Conflicting results with Terlipressin and Nitroglycerin

Pharmacotherapy 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 Synthetic somatostatin analogue - Octreotide Half life 1-2 hours More effective than placebo, vasopressin and balloon tamponade Is as effective as endoscopic sclerotherapy and is a safe treatment for acute variceal bleeding

Pharmacotherapy Non selective ß-adrenergic blockers - proprandolol, nadolol or timolol They decrease portal venous inflow by two mechanisms - decreasing cardiac output (ß1 blockade) - splanchnic vasoconstriction (ß2 blockade and unopposed alpha adrenergic activity)

Pharmacotherapy Antibiotic prophilaxis is mandatory - Reduces rate of bacterial infections - Increases survival Blood replacement to target Hematocrit of 25-30% Avoid intravascular over expansion

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 Therapy 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 Surgery prevents rebleeding increases risk of portosystemic encephalopathy no effect on survival

T I P S reduces rebleeding encephalopathy no effect on survival shunt dysfunction