Marinel S. MandapatSenior Intern

Causes of non-variceal UGIB

Forrest Classificationis a classification of upper gastrointestinal

hemorrhage used for purposes of comparison and in selecting patients for endoscopic treatment

It is instrumental when stratifying patients with upper gastrointestinal hemorrhage into high and low risk categories for mortality.

It is also a significant method of prediction of the risk of rebleeding and very often is used for evaluation of the endoscopic intervention modalities

FORREST CLASSIFICATIONForrest class Type of lesion Risk of

bleedingType I: Active BleedIA Arterial spurting bleeding 100%IB Arterial oozing bleeding 55% (17-100%)Type II: Recent BleedIIA Visible vessel 43% (8-81%)IIB Sentinel clot 22% (14-36%)IIC Hematin covered flat spot 10% (0-13%)Type III: Lesion w/o BleedingIII No stigmata of hemorrhage 5% (0-10%)

Forrest 1a Spurting bleeding

Forrest 1b Non-spurting active bleeding

Forrest 2a Non-bleeding visible vessel

Forrest 2b Non-bleeding ulcer with an adherent clot

Forrest 2c Ulcer with haematin-covered base

Forrest 3 Ulcer with clean base

ENDOSCOPIC MANAGEMENTAdrenaline injection results in haemostasis in up

to100% of patients with bleeding peptic ulcers, probably by a combination of vascular tamponade and vasoconstriction, with a concomitant reduction in re-bleeding rates from 40 to 15%.

The dose of adrenaline required to achieve haemostasis is variable but larger volumes (13–20ml vs. 5–10ml) in high risk patients (Forrest type I or IIa lesions) results in less re-bleeding (15.4% vs. 30.8%).24 Although injection with adrenaline is successful in achieving initial haemostasis, 15-36% of patients rebleed

ENDOSCOPIC MANAGEMENTSclerosants such as ethanol, polidocanol and

ethanolamine are equally effective as adrenaline but carry more risk.

Combination therapy with adrenaline and ethanol may improve haemostasis and shorten hospital stay for patients with spurting haemorrhage.

Repeated daily injection of fibrin glue following treatment with dilute adrenaline in patients with active bleeding or NBVV until the ulcer base is clean or covered is expensive but reduces re-bleeding although not mortality rates.

ENDOSCOPIC MANAGEMENTN-butyl-2-cyanoacrylate (Histoacryl) injection

has been shown to be effective for control of variceal bleeding

More recently, Lee et al demonstrated significantly lower re-bleeding rate for patients with Forrest type Ia lesions treated with Histoacryl compared to injection with hypertonic saline-adrenaline injection. However, there was no overall benefit in the use of Histoacryl with regards to haemostasis rates, emergency surgery or mortality.

ENDOSCOPIC MANAGEMENTIn contrast to injection techniques, thermal

haemostasis is achieved by compression of the artery during heating (coaption) and/or the effect of heat on tissue. The only non-contact thermal techniques currently available are Argon Plasma Coagulation (APC) and laser (Nd:YAG).

APC involves conduction of a high frequency electrical current through a beam of ionized argon gas, resulting in superficial tissue damage and coagulation. A prospective observational study of APC in 254 patients with non-variceal UGIB revealed initial haemostasis rates of 75.9% and re-bleeding rates of 5.7%. The addition of a second haemostasis technique increased successful haemostasis to 99.6%.

ENDOSCOPIC MANAGEMENTBipolar Electrocoagulation (BPE) and Heater

Probe Thermocoagulation (HPT) use thermal. BPE reduces the re-bleeding rate when compared with normal saline injection in high risk bleeding ulcers, and compared to medical therapy when used in combination with adrenaline in Forrest IIb ulcers. Combination therapy with HPT and adrenaline in the treatment of actively bleeding peptic ulcers resulted in haemostasis in up to 98.6%, with re-bleeding in 8.2%, although added benefit is confined to high risk lesions.

When used alone, HPT was not superior to combination treatment with adrenaline and polidocanol in patients with Forrest type I, IIa and IIb ulcers.

ENDOSCOPIC MANAGEMENTMechanical haemostasis with endoloops or

clips, e.g. the Hemoclip (Teleflex Medical, PA), has an increasing role in the control of non-variceal UGIB. Endoclips are deployed on a visible vessel to achieve vascular compression and can achieve homeostasis in up to 100% of cases. Comparative studies suggest lower re-bleeding rates than adrenaline injection, ethanolor saline/adrenaline injection.

ENDOSCOPIC MANAGEMENTEndoscopic band ligation (EBL) is currently

technically easier to use than endoclips and has been shown to be safe and effective for control of small lesions in a small series of acute peptic ulcer bleeding and with bleeding due to Dieulafoy's lesions.

ADHERENT CLOTAdrenaline injectionShaving of the clot with cold guillotineBipolar electrocoagulation of the underlying

ulcer stigmata of recent hemorrhage

ACID SUPPRESSIONIn vitro studies of the effect of gastric pH on

platelet aggregation and coagulation provide the rationale for acid suppression in UGIB.

If gastric pH is maintained above pH6 (by infusional PPI), platelet aggregation is optimized and fibrinolysis relatively inhibited, thereby potentially improving the likelihood of clot stability at an ulcer site.

Acid Neutralizing/Inhibitory DrugsAntacids-rarely used, often used by patients

for symptomatic relief of dyspepsiaH2 receptor antagonists-used for 4-6 weeks

in combination with antibiotics Cimetidine-initial 300 mg qid or 800 mg hs

May have a weak anti-androgenic side effects resulting in reversible gynecomastia and impotence

Ranitidine-300 mg hs Famotidine-40 mg hs Nizatidine-300 mg hs

Acid Neutralizing/Inhibitory DrugsPPIs (e.g. omeprazole, esomeprazole,

lansoprazole, rabeprazole, pantoprazole)-substituted benzimidazole derivatives that covalently bind and irreversibly inhibit H, K-ATPaseRapid onset of action with a max. inhibitory

effect 2-6 h after administration & duration of inhibition up to 72-96h.

Half life ˜18h thus it can take 2-5 days for gastric acid secretion to return to normal levels once these drugs have been discontinued

Cytoprotective AgentsSucralfate-complex sucrose salt in w/c the

hydroxyl groups have been substituted by aluminum hydroxide and sulfateAluminum hydroxide dissociates, leaving the

polar sulfate anion, w/c can bind to positively charged tissue proteins found within the ulcer bed, providing a physico-chemical barrier

May also induce a trophic effect by binding growth factors such as EGF, enhance prostaglandin synthesis, stimulate mucous and bicarbonate secretion, and enhance mucosal defense and repair

Cytoprotective AgentsBismuth-containing preparations-

(e.g.colloidal bismuth subcitrate (CBS) and bismuth subsalicylate (BSS))Ulcer coating; prevention of further

pepsin/HCl-induced damage; binding of pepsin; stimulation of prostaglandins, bicarbonate, and mucous secretion

TreatmentCytoprotective AgentsProstaglandin Analogues (e.g. Misoprostol)

Enhance mucous bicarbonate secretion, stimulate mucosal blood flow, and decrease mucosal cell turnover

Therapeutic dose is 200 µg qid

H. Pylori TherapyTRIPLE THERAPY

1. BSS + Metronidazole + Tetracycline

2. Ranitidine bismuth citrate + Tetracycline + Clarithromycin or Metronidazole

3. Omeprazole (lanzoprazole) + Clarithromycin + Metronidazole or Amoxicillin

2 tabs qid + 250 mg qid + 500 mg qid

400 mg bid + 500 mg bid + 500 mg bid

20 mg bid (30 mg bid) + 250 or 500 mg bid + 500 mg bid or 1 gr bid

QUADRUPLE THERAPY

Omeprazole (lanzoprazole)BSSMetronidazoleTetracycline

20 mg (30 mg) daily2 tabs qid250 mg qid500 mg qid

NSAID-Related Gastric or Duodenal Injury TherapyClinical Setting Recommendation

Active Ulcer NSAID discontinued NSAID continued

H2 receptor antagonist or PPIPPI

Prophylactic Therapy MisoprostolPPISelective COX-2 inhibitor

H. Pylori infection Eradication if active ulcer present or there is a past history of PUD

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