Management of Management of PUD, H. pylori PUD, H. pylori

infectioninfection44thth Med Pharmacology Med Pharmacology

27/10/0527/10/05

IntroductionIntroduction

PUD = ulceration of gastroduodenal mucosa PUD = ulceration of gastroduodenal mucosa (usually extending through muscularis mucosa)(usually extending through muscularis mucosa)

Prevalence 5-10%Prevalence 5-10% 50% of these have recurrence within 5 yrs50% of these have recurrence within 5 yrs Discovery of H. pylori of great importance Discovery of H. pylori of great importance

diagnostically & therapeutically in PUD (Nobel diagnostically & therapeutically in PUD (Nobel prize-Marshall & Warren)prize-Marshall & Warren)

H. pylori cultured from stomach of ~90% DU H. pylori cultured from stomach of ~90% DU pts & ~80% GU ptspts & ~80% GU pts

Eradication of H. pylori Eradication of H. pylori ↓ recurrence of PUD ↓ recurrence of PUD by ~75-90%by ~75-90%

Pathogenesis of PUDPathogenesis of PUD

Not fully understood, but 3 major factors identifiedNot fully understood, but 3 major factors identified

FactorFactor Treatment approachTreatment approach

Infection with gram-Infection with gram-negative H. pylorinegative H. pylori

Eradication of H. pylori Eradication of H. pylori infection, e.g. triple txinfection, e.g. triple tx

↑ ↑ gastric HCl secretiongastric HCl secretion ↓ ↓ HCl secretion or HCl secretion or neutralizing it, e.g. H2 neutralizing it, e.g. H2 antagonists, pirenzepine, antagonists, pirenzepine, antacids antacids

Inadequate mucosal Inadequate mucosal defence against gastric HCldefence against gastric HCl

Agents that protect gastric Agents that protect gastric mucosa, e.g. sucralfatemucosa, e.g. sucralfate

Importance of treating PUDImportance of treating PUD

Gastric ulcers:Gastric ulcers: 5% malignant 5% malignant Endoscopic biopsy at time of initial diagnosis Endoscopic biopsy at time of initial diagnosis recommended & repeat endoscopy after 6-8 wks txrecommended & repeat endoscopy after 6-8 wks txSurgical tx for nonhealing GUSurgical tx for nonhealing GU

Duodenal ulcers:Duodenal ulcers:Usually not malignantUsually not malignantIf pt asymptomatic do not need to prove ulcer healingIf pt asymptomatic do not need to prove ulcer healingMany heal without txMany heal without txH2-receptor antagonists, sucralfate & high dose antacids H2-receptor antagonists, sucralfate & high dose antacids shown to shown to ↑ rate of healing and % of ulcers that heal. ↑ rate of healing and % of ulcers that heal. Drug tx has 70-85% incidence ulcer healing at 6 wks cf Drug tx has 70-85% incidence ulcer healing at 6 wks cf placebo (~40%)placebo (~40%)

Importance of treating PUD Importance of treating PUD (contd)(contd)

Complications of PUDComplications of PUD

1)1) GI bleedingGI bleeding

2)2) Gastric outlet obstructionGastric outlet obstruction

3)3) PerforationPerforation

4)4) Penetration into pancreasPenetration into pancreas

5)5) IntractabilityIntractability

StomachStomach

StomachStomach

DuodenumDuodenum

Non-pharmacological measures to treat Non-pharmacological measures to treat PUDPUD

DietDiet

Stop smokingStop smoking

Avoid aspirin/NSAIDs. Enteric coating or anti-Avoid aspirin/NSAIDs. Enteric coating or anti-ulcer tx may ulcer tx may ↓ mucosal damage from aspirin. In ↓ mucosal damage from aspirin. In pts with strong indications for NSAID tx treating pts with strong indications for NSAID tx treating with PPI, H2-R antagonists, sulcralfate or with PPI, H2-R antagonists, sulcralfate or misoprostil may relieve symptoms. Tx with a COX misoprostil may relieve symptoms. Tx with a COX 2 selective NSAID [CI CVS problems]2 selective NSAID [CI CVS problems]

Avoid C2H5OHAvoid C2H5OH

Drugs used to treat PUD

AntimicrobialAgents

AmoxicillinBismuth

ClarithromycinMetronidazoleTetracycline

H2-HistamineR Blockade

CimetidineFamotidineNizatidineRanitidine

MucosalProtective

Agents

BismuthSulcralfate

Antacids

Al(OH)3[Mg(OH)2]

CaCO3

AntimuscarinicAgents

Pirenzepine

PPI

LansoprazoleOmeprazole

Prostaglandins

Misoprostol

H. pylori EradicationH. pylori Eradication

If GU/DU identified by upper endoscopy/radiographic If GU/DU identified by upper endoscopy/radiographic study need to determine if H.pylori presentstudy need to determine if H.pylori present

Diagnostic tests include:Diagnostic tests include:

1)1) Serologic testingSerologic testing

2)2) C-13 urea breath testC-13 urea breath test

3)3) Urease assay (Clotest)Urease assay (Clotest)

4)4) Culture/histological analysis of endoscopic biopsyCulture/histological analysis of endoscopic biopsy

Majority of PU can be healed with H2-antagonists/PPI Majority of PU can be healed with H2-antagonists/PPI alone, but relapse of sx occur in up to 80% pts within alone, but relapse of sx occur in up to 80% pts within 1 yr cf 8% if treated with H.pylori eradication tx.1 yr cf 8% if treated with H.pylori eradication tx.

Current recommendations for tx of Current recommendations for tx of H. pylori H. pylori

Test for H.pylori before starting eradication txTest for H.pylori before starting eradication tx

If H. pylori test is positive, use eradication tx If H. pylori test is positive, use eradication tx

If H. pylori test is negative, treat with If H. pylori test is negative, treat with lansoprazole (Zoton) 30mg OD. Use for 4 wks for lansoprazole (Zoton) 30mg OD. Use for 4 wks for DU, 8 wks for GU. May use lansoprazole 15mg OD DU, 8 wks for GU. May use lansoprazole 15mg OD to prevent relapseto prevent relapse

Eradication of H. pyloriEradication of H. pyloriEradication defined as negative tests for the Eradication defined as negative tests for the bacterium 4 wks or more after the end of txbacterium 4 wks or more after the end of tx

Current recommendations for tx of Current recommendations for tx of H. pylori H. pylori

1st line eradication tx 1st line eradication tx for H. pylorifor H. pylori

22ndnd line tx line tx

Preferred tx= PPI PO + Preferred tx= PPI PO + Clarithromycin 500mg BD PO Clarithromycin 500mg BD PO + Amoxicillin 1 gm BD PO for 7 + Amoxicillin 1 gm BD PO for 7 daysdays

If Penicillin allergic= PPI + If Penicillin allergic= PPI + Clarithromycin 500mg BD PO Clarithromycin 500mg BD PO + Metronidazole 400mg BD PO + Metronidazole 400mg BD PO for 7 daysfor 7 days

E.g. of PPI: Lansoprazole 30mg E.g. of PPI: Lansoprazole 30mg BD POBD PO

PPI + Bismuth 120mg QDS PO PPI + Bismuth 120mg QDS PO + Metronidazole 500mg TDS + Metronidazole 500mg TDS PO + Tetracycline 500mg QDS PO + Tetracycline 500mg QDS PO for 7 daysPO for 7 days

Subsequent failures handled Subsequent failures handled on individual basis with advice on individual basis with advice from gastro/microfrom gastro/micro

H. pylori eradicationH. pylori eradication

1 week triple-therapy regimens eradicate H.. 1 week triple-therapy regimens eradicate H.. Pylori in >90% cases. Usually no need for Pylori in >90% cases. Usually no need for continued antisecretory tx unless ulcer continued antisecretory tx unless ulcer complicated by bleeding/perforationcomplicated by bleeding/perforation

2 week triple-therapy offer higher eradication 2 week triple-therapy offer higher eradication rates cf 1 week but SE common & poor rates cf 1 week but SE common & poor compliancecompliance

2-week dual-therapy with PPI & antibacterial 2-week dual-therapy with PPI & antibacterial produce low rates of H. pylori eradication & produce low rates of H. pylori eradication & not recommendednot recommended

H. pylori eradicationH. pylori eradication

Treatment failure may be due toTreatment failure may be due to

- Resistance to antibacterial drugs- Resistance to antibacterial drugs

- Poor compliance- Poor compliance

DrugDrug Side effectsSide effects

BismuthBismuth n&v, unpleasant taste, darkening of tongue & stools, n&v, unpleasant taste, darkening of tongue & stools, caution in renal diseasecaution in renal disease

MetronidaMetronidazolezole

n&v, unpleasant taste, n&v, unpleasant taste, ↓effectiveness OCP, care ↓effectiveness OCP, care with lithium/warfarinwith lithium/warfarin

Amoxicillin Amoxicillin

& & tetracyclintetracyclinee

GI side effects, GI side effects, ↓ effectiveness OCP, ↓ effectiveness OCP, pseudomenbranous colitispseudomenbranous colitis

LansoprazLansoprazoleole

↓ ↓ effectiveness OCPeffectiveness OCP

H2-receptor antagonistsH2-receptor antagonists

MOA:MOA: Competitively block binding of histamine Competitively block binding of histamine to H2 R, to H2 R, ↓ intracellular cAMP & secretion of ↓ intracellular cAMP & secretion of gastric acid. Reversiblegastric acid. Reversible

Egs: Cimetidine, ranitidine, famotidine & Egs: Cimetidine, ranitidine, famotidine & nizatidinenizatidine

Effective for acute/chronic DU & benign GU. Effective for acute/chronic DU & benign GU. Recurrence common after tx with H2-R Recurrence common after tx with H2-R antagonists alone is stopped. antagonists alone is stopped.

Mainly renal excretionMainly renal excretion

H2-receptor antagonistsH2-receptor antagonists

DrugDrug Side effectsSide effects

CimetidineCimetidine -reversible impotence, -reversible impotence, gynaecomastia & gynaecomastia & ↓ sperm count ↓ sperm count (high doses) (nonsteroidal (high doses) (nonsteroidal antiandrogen)antiandrogen)

-mental status abnormalities--mental status abnormalities-confusion, hallucinations confusion, hallucinations (elderly/renal impairment)(elderly/renal impairment)

-leukopenia & thrombocytopenia -leukopenia & thrombocytopenia (rare)(rare)

-cytochrome P450 inhibitor (e.g. -cytochrome P450 inhibitor (e.g. impairs metabolism of warfarin, impairs metabolism of warfarin, theophylline & phenytoin)theophylline & phenytoin)

Ranitidine, fanotidine, nizatidineRanitidine, fanotidine, nizatidine -Impotence, gynaecomastia & -Impotence, gynaecomastia & confusion less frequently than confusion less frequently than cimetidine.cimetidine.

-Little interference with -Little interference with cytochrome P450cytochrome P450

-Reversible drug-induced -Reversible drug-induced hepatitis with all H2-antagonistshepatitis with all H2-antagonists

Proton-pump Inhibitors (PPI)Proton-pump Inhibitors (PPI)

• MOA: blocks parietal cell HMOA: blocks parietal cell H+/K+ ATPase +/K+ ATPase enzyme system (proton pump) ↓ secretion of enzyme system (proton pump) ↓ secretion of H+ ions into gastric lumenH+ ions into gastric lumen

• Heals erosive oesophagitis more effectively Heals erosive oesophagitis more effectively than H2-antagonists. Used in antimicrobial than H2-antagonists. Used in antimicrobial regimens to eradicate H. pyloriregimens to eradicate H. pylori

• SE: n&v, diarrhoea, dizziness, headaches, SE: n&v, diarrhoea, dizziness, headaches, gynaecomastia & impotence (rare), gynaecomastia & impotence (rare), thrombocytopenia, rashesthrombocytopenia, rashes

• Dose: 20mg/day omeprazole in acute tx of DUDose: 20mg/day omeprazole in acute tx of DU

Mucosal Protective AgentsMucosal Protective Agents

1)1) SulcralfateSulcralfateMOA: Binds to positively charged proteins present on MOA: Binds to positively charged proteins present on damaged mucosa forming a protective coatdamaged mucosa forming a protective coatUseful in “stress ulceration”Useful in “stress ulceration”As effective as H2-R antagonists/high dose antacids in As effective as H2-R antagonists/high dose antacids in healing of DUhealing of DUSE: ConstipationSE: Constipation ↓↓absorption of cimetidine, digoxin, phenytoin & absorption of cimetidine, digoxin, phenytoin & tetracyclinetetracycline

2)2) BismuthBismuthMOA: Antimicrobial action. Also inhibit pepsin activity, MOA: Antimicrobial action. Also inhibit pepsin activity, ↑mucus secretion & interact with proteins in necrotic ↑mucus secretion & interact with proteins in necrotic mucosal tissue to coat & protect the ulcer cratermucosal tissue to coat & protect the ulcer crater

AntacidsAntacids

• MOA: Weak bases that MOA: Weak bases that react with gastric acid react with gastric acid to form H20+salt. to form H20+salt. ↓pepsin activity as ↓pepsin activity as pepsin inactive at pH>4pepsin inactive at pH>4

• Symptom relief, Symptom relief, liquids>tabletsliquids>tablets

• E.g. Maalox = E.g. Maalox = [Mg(OH)2] + Al(OH)3[Mg(OH)2] + Al(OH)3

DrugDrug Side effectSide effect

[Mg(OH)2][Mg(OH)2] severe osmotic severe osmotic diarrhoea diarrhoea (therefore (therefore combined with combined with AlOH)AlOH)

Al(OH)3Al(OH)3 ↓↓phosphate, phosphate, ↓absorption of ↓absorption of tetracycline, tetracycline, thyroxine & thyroxine & chlorpromazinechlorpromazine, constipation, constipation

CaCO3CaCO3 ↑↑Ca in blood & Ca in blood & urine (high urine (high doses)doses)

Antimuscarinic drugsAntimuscarinic drugs

• Not successful b/c of general unwanted antimuscarinic effectsNot successful b/c of general unwanted antimuscarinic effects

• Muscarinic R stimulation Muscarinic R stimulation ↑ GI motility & secretory activity↑ GI motility & secretory activity

• Pirenzipine:Pirenzipine: Some selectivity due to affinity for & blockade of M1- Some selectivity due to affinity for & blockade of M1-receptors in autonomic ganglia (low affinity for M2-receptors of receptors in autonomic ganglia (low affinity for M2-receptors of smooth muscle of ileum & bladder)smooth muscle of ileum & bladder)

In stomach appears to inhibit transmission in parasympathetic In stomach appears to inhibit transmission in parasympathetic enteric ganglia.enteric ganglia.

Used as adjunct in refractory PUD & Zollinger-Ellison syndrome Used as adjunct in refractory PUD & Zollinger-Ellison syndrome

Poorly absorbed from GIT and excreted mainly unchanged in urine & Poorly absorbed from GIT and excreted mainly unchanged in urine & bilebile

Doesn’t cross BBBDoesn’t cross BBB

SE: Dry mouth, visual disturbances, agranulocytosis & SE: Dry mouth, visual disturbances, agranulocytosis & thrombocytopeniathrombocytopenia

Prostaglandin analoguesProstaglandin analogues

• Endogenous prostaglandins (PGE2 & I2) contribute to GI mucosa Endogenous prostaglandins (PGE2 & I2) contribute to GI mucosa integrity byintegrity by-stimulation of mucus & bicarbonate secretion-stimulation of mucus & bicarbonate secretion-maintenance of blood flow (allows removal of luminal H-ions)-maintenance of blood flow (allows removal of luminal H-ions)-prevention of luminal H-ions from diffusing into the mucosa (e.g. in -prevention of luminal H-ions from diffusing into the mucosa (e.g. in response to C2H5OH)response to C2H5OH)--↓ of gastric acid secretion↓ of gastric acid secretion-helping to repair damaged epithelium-helping to repair damaged epithelium

• Gastric & duodenal mucosal damage & chronic PU associated with the Gastric & duodenal mucosal damage & chronic PU associated with the use ofuse ofNSAIDs may derive from interference with the cytoprotective action ofNSAIDs may derive from interference with the cytoprotective action ofprostaglandinsprostaglandins

• MisoprostolMisoprostol = synthetic prostaglandin E1 analogue = synthetic prostaglandin E1 analogue Prevents NSAID induced ulcers & heals chronic GU & DUPrevents NSAID induced ulcers & heals chronic GU & DUSE: Abdo pain, n&v, diarrhoea, abortifacient (produces uterine SE: Abdo pain, n&v, diarrhoea, abortifacient (produces uterine contractions)contractions)

NSAID-associated ulcersNSAID-associated ulcers

• GI bleed & ulceration can occur with NSAIDs. If possible withdraw GI bleed & ulceration can occur with NSAIDs. If possible withdraw NSAID if ulceration. Consider alternative analgesiaNSAID if ulceration. Consider alternative analgesia

• If at risk of ulcer a PPI, H2-R antagonist or misoprostol may be If at risk of ulcer a PPI, H2-R antagonist or misoprostol may be considered for protection against NSAID-associated ulcers. Colic & considered for protection against NSAID-associated ulcers. Colic & diarrhoea may limit use of misoprostoldiarrhoea may limit use of misoprostol

• If NSAID treatment needs to continueIf NSAID treatment needs to continue-treat ulcer with PPI & on healing of ulcer continue with PPI-treat ulcer with PPI & on healing of ulcer continue with PPI-treat ulcer with PPI & on healing switch to misoprostol for -treat ulcer with PPI & on healing switch to misoprostol for maintenance txmaintenance tx

Caution COX-2 inhibitors & CVS eventsCaution COX-2 inhibitors & CVS eventsBecause of concerns re CVS safety, COX-2 inhibitors should only be used Because of concerns re CVS safety, COX-2 inhibitors should only be used

in in preference to standard NSAIDs only when specifically indicated & afterpreference to standard NSAIDs only when specifically indicated & afterassessment of CVS. assessment of CVS. Pts receiving COX-2 inhibitor & who have IHD or cerebrovascularPts receiving COX-2 inhibitor & who have IHD or cerebrovasculardisease should be switched to alternative asapdisease should be switched to alternative asap

Associated Gastric ConditionsAssociated Gastric Conditions

Zollinger-ellison syndromeZollinger-ellison syndromeRare gastrin-secreting, non-Rare gastrin-secreting, non-ß islet cell tumour of the pancreas or ß islet cell tumour of the pancreas or duodenum →gastric acid hypersecretionduodenum →gastric acid hypersecretion2/32/3rdrd Zollinger-ellison tumours malignant Zollinger-ellison tumours malignantMEN-1 associated with Zollinger-ellison syndrome in ¼ casesMEN-1 associated with Zollinger-ellison syndrome in ¼ casesPresents with DU (single/multiple) + diarrhoeaPresents with DU (single/multiple) + diarrhoeaTx: Control of ↑acid with H2-R antagonists & PPI at much higher Tx: Control of ↑acid with H2-R antagonists & PPI at much higher doses than those used for PUDdoses than those used for PUD

Non-ulcer dyspepsiaNon-ulcer dyspepsiaSyndrome of persistent ulcer-like symptoms in absence of Syndrome of persistent ulcer-like symptoms in absence of radiographic & endoscopic abnormalitiesradiographic & endoscopic abnormalitiesMay be explained by motor abnormalities, microscopic May be explained by motor abnormalities, microscopic inflammation, H. pylori-associated gastritis & associated psychiatric inflammation, H. pylori-associated gastritis & associated psychiatric diseasediseaseTx: Empiric. Some may benefit from psychoactive agents e.g. TCADsTx: Empiric. Some may benefit from psychoactive agents e.g. TCADs

GORDGORD

GORD = Symptoms of “heartburn”GORD = Symptoms of “heartburn”

General advice includes General advice includes AVOIDINGAVOIDING

Drug TxDrug Tx

Meals at night, lying down after Meals at night, lying down after mealsmealsElevate head of bedElevate head of bedHeavy lifting, tight clothing, Heavy lifting, tight clothing, bending bending Being overweightBeing overweightSmoking (nicotine relaxes lower Smoking (nicotine relaxes lower oesophageal sphincter)oesophageal sphincter)Aggravating substances (spicy Aggravating substances (spicy foods, C2H5OH)foods, C2H5OH)Drugs which encourage reflux Drugs which encourage reflux (e.g. antimuscarinic, smooth (e.g. antimuscarinic, smooth muscle relaxants, theophylline)muscle relaxants, theophylline)

antacids=+/-alginic acidantacids=+/-alginic acidPro-kinetic agent, e.g. Pro-kinetic agent, e.g. metoclopramidemetoclopramideH2-antagonistH2-antagonistPPIPPIIf severe sx when tx stopped, or If severe sx when tx stopped, or bleed from oesophagitis or bleed from oesophagitis or stricture maintenance tx with PPI stricture maintenance tx with PPI or surgery may be necessaryor surgery may be necessary

GI haemorrhageGI haemorrhage

Risk factors for ↑ morbidity/mortalityRisk factors for ↑ morbidity/mortality1)1) Age > 60yrsAge > 60yrs2)2) Additional co-morbid illness/esAdditional co-morbid illness/es3)3) Bright red haemetemesis & Bright red haemetemesis & ↓ BP↓ BP4)4) Large (>2 cm ulcers)Large (>2 cm ulcers)5)5) ShockShock6)6) Recurrent bleedRecurrent bleed

Need to maintain adequate circulatory volume in order to localise Need to maintain adequate circulatory volume in order to localise bleeding site and institute txbleeding site and institute tx

Management of upper GI haemorrhageManagement of upper GI haemorrhage

1) Resuscitation and stabilisation1) Resuscitation and stabilisationAssess haemodynamic statusAssess haemodynamic statusFrequent vital signs HR & BPFrequent vital signs HR & BPBlood for FBC, coag, grp & cross-matchBlood for FBC, coag, grp & cross-match

GI haemorrhage (contd)GI haemorrhage (contd)

2)2) TxTx IVF. Hypovolaemia is usually the cause of the IVF. Hypovolaemia is usually the cause of the ↓BP so should initiate ↓BP so should initiate

restoration of intravascular volume. Vasopressors generally not restoration of intravascular volume. Vasopressors generally not indicated.indicated.

Blood transfusion if bleeding massive, ongoing or severeBlood transfusion if bleeding massive, ongoing or severe Coagulopathy may require FFPCoagulopathy may require FFP Thrombocytopenia may require platelet transfusionThrombocytopenia may require platelet transfusion ET intubation to prevent aspirationET intubation to prevent aspiration CVP monitoring to guide fluid replacementCVP monitoring to guide fluid replacement Early consult with gastroenterologist, surgeon, or invasive radiologist Early consult with gastroenterologist, surgeon, or invasive radiologist

when significant haemorrhage, continued instability or active when significant haemorrhage, continued instability or active bleedingbleeding

3)3) Upper GI bleeding diagnosed byUpper GI bleeding diagnosed by• OGD (diagnostic &/or therapeutic)OGD (diagnostic &/or therapeutic)• ArteriographyArteriography• Upper GI barium studyUpper GI barium study

Treatment of different lesionsTreatment of different lesions

Peptic ulcer haemorrhagePeptic ulcer haemorrhageMost stop bleeding spontaneouslyMost stop bleeding spontaneously

1)1) Endoscopy – thermal coagulation, injection tx, haemostatic clipsEndoscopy – thermal coagulation, injection tx, haemostatic clips

2)2) Surgery – e.g. if failure of endoscopic tx, haemodynamic instability Surgery – e.g. if failure of endoscopic tx, haemodynamic instability despite resuscitation, recurrent haemorrhage, shock, continued despite resuscitation, recurrent haemorrhage, shock, continued bleed requiring > 3 units/day. Tx include oversewing of artery + bleed requiring > 3 units/day. Tx include oversewing of artery + truncal vagotomy + pyloroplasty, antrectomy, gastrojejunostomy truncal vagotomy + pyloroplasty, antrectomy, gastrojejunostomy (Billroth procedure), highly selective vagotomy(Billroth procedure), highly selective vagotomy

3)3) Arterial angiotherapy (arterial vasopressin/embolisation)Arterial angiotherapy (arterial vasopressin/embolisation)

4)4) Intravenous PPI. Better able to maintain gastric pH > 6 & protect Intravenous PPI. Better able to maintain gastric pH > 6 & protect ulcer clot from fibrinolysisulcer clot from fibrinolysis

5)5) H2-antagonists. Not in active bleed. ?effective in H2-antagonists. Not in active bleed. ?effective in ↓recurrent bleed↓recurrent bleed

Treatment of different lesionsTreatment of different lesions

Mallory-Weiss tear:Mallory-Weiss tear: Mucosal tear at GO junction. Most stop spontaneously. May need Mucosal tear at GO junction. Most stop spontaneously. May need

therapeutictherapeuticendoscopy or arterial angiographyendoscopy or arterial angiography

Aortoenteric fistula:Aortoenteric fistula: Usually aorto-duodenal. Usually hx previous aortic graft surgery. Tx: Usually aorto-duodenal. Usually hx previous aortic graft surgery. Tx:

surgerysurgery

Stress ulceration:Stress ulceration: Pts with head injuries, burns, major trauma, shock, sepsis, Pts with head injuries, burns, major trauma, shock, sepsis,

respiratory failure,respiratory failure,coagulopathy.coagulopathy.Prophylactic tx with H2-R antagonists, sucralfate & antacids in pts Prophylactic tx with H2-R antagonists, sucralfate & antacids in pts

at riskat risk