Consensus Approach to Non Variceal Upper GI Bleeding

Dr Yasser Abu SafiehAss Prof Of Medicine and Gastroenterology, member

of AGA & ASGE, SAH Hospital, Nablus

14-15/10/2010 Ramalla, Jerusalem

Outlines

• Resuscitation and risk stratification

• Endoscopic Treatment

• The role of PPI

Overall management

ABC and adequate Resuscitation

Early risk stratification Pre-endoscopy and

at endoscopy

All other pts Admit

Very Low risk pt High risk pt low risk pts

discharge home Endoscopic hemostasis

Initiate IV PPI high dose

consider 2nd prophylaxis: H pylori

NSAID, ASA Clopidogrel

Initial Resuscitation

• Appropriate critical paths and equipment/ human resources ( including after- hour assistance) should be in place

• Immediately evaluate and initiate appropriate resuscitation

• Blood transfusions should be administered to a pt. with Hb <7 gm/dl

Rockall Score – Risk assessment of Death/Rebleeding (N=4185)

Variable 0

Score 1

2

3

Age (yrs) < 60 60-79 ≥ 80

Hemodynamic status

No shockP < 100Syst BP ≥ 100

P ≥ 100 plusSys BP ≥ 100

Hypotension

Diagnosis MW tear, normal endoscopy with no blood seen

All other diagnosis Malignancy of UGI tract

Major SRH None or dark spot Blood in UGI tractAdherent clot, visible or spurting vessel

Comorbidity No or mild coexisting

Moderate coexisting (e.g., hypertension)

Severe coexisting (e.g., CHF)

Life threatening (e.g., RF)

Rockall, Lancet 1996

IV Erythromycin/ MetoclopromideNaso-Gastric tube

• Sampling of luminal contents helpful

• NG lavage RCT- proven, yet requires oro-gastric insertion of large-bore tube(airway)

• Also decrease likelihood of blood in stomach

• No improvement in, mortality, re-bleeding transfused units, or surgery

• Should not be used routinely, selected pts

• EKG is needed before erythromycin(QT)

UGB-Endoscopic Findings

PUD56%

Other30%

Esophagitis

8%

M-W tear

4%

Dieulafoy

2%oozing22%

visiblevessel14%

clean base46%

other

Spurting

3%

clot

7%

spot

4%

2484 procedures in 1869 patients

Endoscopy performed within 24 hrs in 76%

Barkun et al., Am J Gastroenterol. 2004

The benefits of early endoscopy

Early Endoscopy(first24 hrs) allows for: safe and prompt discharge pts classified low risk

improves pt outcomes for pts classified as high risk (blood transfusion, LOS)

reduces resources utilization for pts classified either low or high risk

Recent observational data suggest early endoscopy decreases the need for surgery and may improve mortality

NVUGIB pts admitted on weekends had a higher adjusted in-hospital mortality Barkun,2003, Shaheen,2009,Cooper 2009

Endoscopic FindingsForrest Grade and Description, Preval %

Re-bleeding Rate % Mortality %

GIII -Clean Base ( 42%) 5% 2%

GIIc- Black spot (20%)GIIb- NBVV+clot (17%)

10% 22%

3% 7%

GIIa – NBVV (17%) 43% 11%

GIa- Active spurter (18%)GIb-Active oozing 55% 11%

Clean Base,III

Black Spot, IIc

NBVV, IIaOozing, IbSpurter, Ia

Prognostic Factors: Endoscopic

Laine, Peterson, N Engl J Med 1994.

5%10%

22%

43%

55%

0%

20%

40%

60%

80%

% o

f p

ati

en

ts r

eb

lee

din

g

Clean base Flat spot Adherentclot

Nonbleedingvisiblevessel

Activebleeding

Ia = spurterIa = spurterIb = oozerIb = oozer

IIaIIaIIbIIb

ForrestForrest

Incidence of Re-bleeding by Appearance of Ulcer at EndoscopyIncidence of Re-bleeding by Appearance of Ulcer at Endoscopy

Range of Reported Percentages of RecurrentBleeding With Predictive Factors to Failure WithEndoscopic Hemostatic Treatment Modified from Elmunzer et al

Predictive Factors Range Of percentages in patients Re-bleeding

Hemodynamic instability 19.2-47.1%

Active bleeding 12.1-48.9%

Large ulcer size>2cm 14.8-36.3%

Post DU

Large curve GU

43-57.1%

22.9-35%.

Who can be sent home from the emergency room

Proposed Selection Criteria for an Abbreviated Hospital Stay or Outpatient Treatment of Patients at Low Risk.*Criteria

1-Age, <60 yr

2-Absence of hemodynamic instability, which is defined as resting tachycardia

(pulse, ≥100 beats per minute), hypotension (systolic blood pressure,

< 100 mm Hg), or postural changes (increase in pulse of ≥20 beats per

minute or a drop in systolic blood pressure of ≥20 mm Hg on standing,(

or hemodynamic stability within 3 hours after initial evaluation

3-Absence of a severe coexisting illness (e.g., heart failure, chronic obstructive

pulmonary disease, hepatic cirrhosis, hematologic cancer, chronic renal

failure, and cerebrovascular accident(

4-A hemoglobin level of more than 8 to 10 g per deciliter after adequate intravascular

volume expansion and no need for blood transfusion

5-Normal coagulation studies

6-Onset of bleeding outside the hospital

7-Presence of a clean-base ulcer or no obvious endoscopic finding on early endoscopy

) performed within 24 hours after presentation(

8-Adequate social support at home with the ability to return promptly to a hospital

Hemostatic modalities

Which is the best endoscopic hemostatic modality?

Not epinephrine injection alone Thermal therapy, sclerosant therapy, clips,

and thrombin/ fibrin glue all appear to be effective endoscopic hemostatic therapies

Thermal alone OR clips alone As good as injection+thermal?

Sung Gut 2007,Laine, CGH2009, BarkunGIE,2009

COMBINATION ENDOSCOPIC THERAPY

+

Injection Thermalfollowed by

Clipping a visible vessel / oozer

Why controversy about adherent clot• A finding of clot in an

ulcer bed warrants targeted irrigation in attempt at dislodgment, with an appropriate Rx of the underlying lesion.

• Marked variability in study design

• Laine Gastro 2005129, 2127• Kahi gastro2005 129,855

• In a pop with rates of re-bleeding with clots, endo Rx is likely to decrease re-bleeding

• High quality blinded trials indicate that the use of modern intensive PPIRx without endo Rx in pts with clots may result in extremly low rates of rebleeding(0/86, 2 studies

What About elevated INR and endoscopy

• A presenting INR<1.5 does not predict re-bleeding yet is an independent predictor of subsequent death following an admission due to NVUGIB

• Correction of INR to 1.8 as part of intensive resuscitation measures may improve mortality

• Endoscopy Rx may be safely performed in pts with an INR of<2.5

• “ in pts on anticoagulant, correction of coagulopathy is recommended but should not delay endoscopy”

Barkun, DDW 2009

Second look endoscopy

• Re-bleeding was significantly decreased by routine second-look endoscopy.

• BUT when taking into account trial limitations and heterogeneity( both clinical & statistical), and current standard of high-dose iv PPI, this approach should probably be reserved to selected pts at especially high risk of re-bleeding

PPI pre-endoscopy, Lau NEJM 2007

OmeprazoleN=314 (187

PUD)

PlaceboN=317 (190

PUD)

P value

Re-bleeding 3.5% (11) 2.5% (8) NS

Surgery 1.6% (3) 2.1% (4) NS

Mortality 2.5% (8) 2.2% (7) NS

Endo Rx 19.1% (60) 28.4% (90) 0.007

Hospital stay < 3 days

60.5% (190) 49.2% (156) .004

Endo stigmata: - Active bleeders - NBVV - Clots - Flat pigments - Clean base

6.4% (12)12.3 (23)3.7% (7)

13.4% (25)64.2% (120)

14.7% (28) 16.3% (31)5.8% (11)

15.8% (30)47.4% (90)

P=0.01NSNSNS

P=0.001

?additional effect of PPI’s?

Cochrane meta-analysis

Effect of PPI on outcomes of pts with PUD bleeding

• PPI improve mortality in pts w HRS only if they have initially undergone endoscopic homeostasis(i.e, mainly high dose iv)

• Also, these findings have been confirmed in a “real-life” setting

• Optimal dose and rout of administration still unclear, but most solid data and recommendation are for high dose IV PPI

So What to Do?Subgroup selection• Efficacy at best marginal, so PPI should NOT

replace the role of adequate resuscitation and early endoscopy

• Can provide PPI before endoscopy or not; more likely to be cost effective IF:

Delay to endoscopy(over 16hours) Pt more likely to be bleeding from a non variceal source

high risk lesion(hematemesis (bloody NGT)

• If you are going to use, high-dose preferred Barkun AN GIE 2008

In patients awaiting endoscopy,

empiric therapy with high dose

proton pump inhibitor should be

considered

Regimen of IV Proton Pump Inhibitor

Omeprazole 80mg then 8mg per hr

Pantoprazole 80mg then 8mg per hr

Esomeprazole 80mgthen 8mg per hr

Lansoprazole 60mg then 8mg per hr

Study PPIn/N

Controln/N

Odds Ratio (fixed)95% CI

Weight(%)

Odds Ratio (fixed)95% CI

01 Initial EHT

Barkun 2004 8/618 14/626 36.6 0.57 (0.24–1.38)

Javid 2001 1/50 2/54 5.0 0.53 (0.05–6.04)

Kaviani 2003 0/71 1/78 3.8 0.36 (0.01–9.01)

Lau 2000 5/120 12/120 30.6 0.39 (0.13–1.15)

Lin 1998 0/50 2/50 6.6 0.19 (0.01–4.10)

Villanoeva 1995 3/45 1/41 2.6 2.86 (0.29–28.62)

Subtotal (95% CI) 954 969 85.2 0.54 (0.30–0.96)

02 Without initial EHT

Brunner 1990 1/19 1/20 2.5 1.06 (0.06–18.17)

Cardi 1997 0/21 0/24 0.0 Not estimable

Khuroo 1997 2/46 5/49 12.3 0.40 (0.07–2.17)

Subtotal (95% CI) 86 93 14.8 0.51 (0.12–2.12)

Total (95% CI) 1040 1062 100.0 0.53 (0.31–0.91)

PPI and UGI bleeding in patients withhigh risk stigmata: Effect on mortality

Favors PPI Favors controlQ01 Q1 10 1001

Leontiadis et al, The Cochrane Database of Systematic Reviews 2006; 1

Excluding patientswith adherent clots

PPI improve mortality in patients w HRS only if they have initially undergone endoscopic haemostasis( mainly high dose IV)

Also, these findings have been confirmed in “a real life” setting

Intravenous Esomeprazole for Prevention of Recurrent Peptic Ulcer Bleeding

A Randomized Trialfor the Peptic Ulcer Bleed Study Group(April 09)

Joseph J.Y. Sung, MAlan Barkun, MD; Ernst J. Kuipers, MD; Joachim Mössner, MD; Dennis M. Jensen, MD; Robert Stuart, MD; James Y. Lau, MD; Henrik Ahlbom, BSc; Jan Kilhamn, MD; tTore Lind, MD; and Tore Lind, MD

Study flow diagram.GI = gastrointestinal; ITT = intention-to-treat; PP = per-protocol.

Sung J J et al. Ann Intern Med 2009;150:455-464

©2009 by American College of Physicians

Kaplan–Meier estimate of the cumulative percentage of patients with recurrent bleeding within 30 days.

Sung J J et al. Ann Intern Med 2009;150:455-464

©2009 by American College of Physicians

High-dose esomeprazole reduce recurrent bleeding in some patients with peptic ulcer ,

Sung J J et al. Ann Intern Med 2009;150:455-464

Why Are I.V. PPIs So Cost-Effective?

NNT: approximately 5–6NNT: approximately 5–6

Medication Cost$240

Medication Cost$240

Additional cost of 1

Rebleeding

$2,524

Additional cost of 1

Rebleeding

$2,524

Other aspects of in-hospital course

• Pt with Low risk, early feeding• Most pts have undergone endoscopic

intervention for HRS should be hospitalized for at least 72 hrs thereafter

• Surgical consultation for patients who have failed endoscopic Rx,

• Percutaneous embolization instead of surgery , in pts having failed endoscopic Rx

Discharge PPI dosing

• Patients should be discharged on single daily dose of PPI for a duration dictated by underlying etiology

• If bleeding from esophagitis consider double dose

• Length of Rx varies according to location of ulcer and use of Aspirin, clopidogrel

Strategies in management of Ulcer Bleeding

Peptic Ulcer Bleeding

Forrest I Forrest II a/b Forrest IIc, III

IV PPIEndo Rx

IV PPI?)IIb(Endo Rx

Oral PPINo Endo Rx

RepeatEndo Rx

Recurrent bleeding

Embolization/Opn

Laine CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2009;7:33–47, Sung. Nature Clinical Practice 2006;3:24-32

Conclusion

• ABC’s and appropriate resuscitation critical• Early risk stratification, including early

endoscopy• Early discharge for very low-risk pts• Endoscopic hemostasis for high-risk lesions • High doses IV PPI, are adjuvant to endoscopic

hemostasis• Secondary prophylaxis needed for pts w :- H pylori or NSAIDs/COX2, ASA/ clopidogrel

THANK YOU