Update on management of Update on management of Acute Non-Variceal Upper GI Acute Non-Variceal Upper GI

Bleeding (UGIB)Bleeding (UGIB)

A Aljebreen, MD, FRCPCA Aljebreen, MD, FRCPC

Objectives

Initial managementInitial managementRole for NG aspirate?Role for NG aspirate?Risk stratificationRisk stratificationRole for pharmacotherapyRole for pharmacotherapyDefinition of urgent endoscopyDefinition of urgent endoscopyEndoscopic managementEndoscopic management

A common medical condition

Acute UGI bleeding is the commonest emergency managed by gastroenterologists.

Incidence ranging from 50-150 per 100 000 of the population each year.

Highest in areas of the lowest socioeconomic status.

Morbidity data

Despite recent advances in therapy, mortality rates have remained essentially unchanged for the past half century at 6-8%Pts are older and consequently more co-

morbidities? Under use of endoscopic hemostatic

techniques.

Barkun et al. Am J Gastroenterol. 2001;96:S261.

Initial management History & physical exam that focuses on

The possible etiology Source (upper vs lower, role of NG aspirate?) & Severity of the bleeding (risk stratification).

Resuscitation (secure airway/ fluids/ PRBCs/ FFP)Resuscitation (secure airway/ fluids/ PRBCs/ FFP) CBC, PT, PTT, cross match, U & E, LFTCBC, PT, PTT, cross match, U & E, LFT Monitor vital signs/ urine outputMonitor vital signs/ urine output Multiple medical subspecialities (internist/ Multiple medical subspecialities (internist/

gastroenterologist/ surgeon/ intensivists)gastroenterologist/ surgeon/ intensivists) Drug therapy?Drug therapy? Urgent endoscopy?Urgent endoscopy?

Etiology of non-variceal UGIB

PUD

errosions

MWT

others

Huang et al, Gastroenterol Clin N Am (2003)

NG role in UGIB

The presence of blood in NG aspirate confirms an upper GI source.

The detection of red blood with an in-and-out NG tube has been shown to predict poor outcome.

NGA is useful in predicting high risk endoscopic NGA is useful in predicting high risk endoscopic lesion (bleeding or non-bleeding visible vessel). lesion (bleeding or non-bleeding visible vessel).

It may help to determine which patients would It may help to determine which patients would benefit from earlier endoscopy.benefit from earlier endoscopy.

Aljebreen et al, GI Endoscopy Feb 2004

Risk stratification

80% of patients will stop bleeding spontaneously without recurrence.

Most morbidity and mortality occur among the remaining 20%.

Thus, ?? identify patients at high risk for an adverse

outcome

A total score of <3 is associated with an excellent prognosis while a score >8 is associated with a high risk of death

Rockall et al. BMJ 1995;311:222–6.

Rockall et al, Lancet. 1996; 347:1138-40

Clinical predictors of re-bleedingRisk factorRisk factorOdds RatioOdds Ratio

Age>65 y>70 y

1.31.3

2.32.3

Shock1.2-3.651.2-3.65

Health status ASA class 11.94-7.361.94-7.36

Comorbid illness1.6-7.631.6-7.63

Erratic mental status3.103.10

Ongoing bleeding3.143.14

Melena1.61.6

Red blood on PR3.763.76

Red blood on NG1.11-11.61.11-11.6

Hematemesis1.2-5.71.2-5.7

Coagulopathy 1.961.96

Barkun et al, Ann Int Med Nov 2003

Endoscopic predictors of rebleeding

Risk factorOdds Ratio

Active bleeding on endoscopy2.5-6.5

Endoscopic HR stigmata1.9-4.8

Clot1.8

Ulcer >2cmUlcer >2cm2.3-3.5

Diagnosis of GU or DUDiagnosis of GU or DU2.7

Ulcer locationUlcer locationHigh on lesser curvatureHigh on lesser curvatureSuperior wallSuperior wallPosterior wallPosterior wall

2.813.99.2

Barkun et al, Ann Int Med Nov 2003

Histamine 2 Receptor Antagonist (H2-RA)

A recent meta-analysis concluded that IV H2-RA provided no additional benefit in bleeding duodenal ulcers but provided small absolute risk reductions in re-bleeding (7.2%), surgery (6.7%), and death (3.2%) in pts e bleeding gastric ulcer.

Recent meta-analyses have found Proton Pump Inhibitors (PPI) to be more effective than H2-RA or placebo in preventing persistent or recurrent bleeding and surgery in selected patients.

Selby et al, Aliment Pharmacol Ther. 2000;14:1119-26. Levine et al, Aliment Pharmacol Ther. 2002;16:1137-42.Zed et al, Ann Pharmacother. 2001;35:1528-34.

Oral PPI? Two studies in Asia compared oral omeprazole, 40 mg

every 12 hours for 5 days, with either placebo (without endoscopic therapy) or endoscopic injection of alcohol for high-risk lesions.

A third study compared the same omeprazole dosage after endoscopic injection therapy with placebo.

All showed decreased re-bleeding with or without decreased rates of surgery.

A study from Iran using oral omeprazole, 20 mg every 6 hours for 5 days also suggested decreased re-bleeding compared with placebo after injection hemostasis.

Khuroo et al, N Engl J Med. 1997;336:1054-8. Jung et al, Am J Gastroenterol. 2002;97:1736-40. Javid et al, Am J Med. 2001;111:280-4.Kaviani et al, Aliment Pharmacol Ther. 2003;17:211-6.

Oral PPI therapy in patients with peptic ulcer bleeding as compared to placebo.

Khouro et al, NEJM, 1997

IV PPI

Four RCTs assessing high-dose bolus and continuous-infusion PPI (high-risk stigmata following endoscopic therapy), have showndecreased re-bleeding and, in some cases, reduced need for surgery compared with H2-

RA or placebo. 80-mg bolus followed by 8 mg/h for 72

hours after endoscopic therapy.

Octereotide?

Not recommended in the routine treatment of Not recommended in the routine treatment of UGIB.UGIB.

A meta-analysis of 14 trials, including 1829 patients treated with somatostatin or octreotide compared with H2-RA or placebo, found a reduced risk for re-bleeding.

In the McGill University meta-analyses by Bardou and colleagues, neither somatostatin nor octreotide improved outcomes compared with other pharmacotherapy or endoscopic therapy.

Imperiale et al, Ann Intern Med. 1997;127:1062-71.

Bardou M, Barkun A. [Abstract]. Gastroenterology. 2003;123:A239.

?urgent Endoscopy

Indications of emergency gastroscopy Indications of emergency gastroscopy (within 6-8 hours):(within 6-8 hours): If pt presented with hemodynamic instability If pt presented with hemodynamic instability

(tachycardic and or hypotension)(tachycardic and or hypotension) If pt presented with few hrs h/o significant If pt presented with few hrs h/o significant

hematemesishematemesis If had Red NG aspirateIf had Red NG aspirate

Why early endoscopy (within 24hrs)?

It allows for safe and prompt discharge of patients

classified as low risk; improves patient outcomes for patients

classified as high risk and reduces resource utilization for patients

classified as either low or high risk

Cipolletta et al, GI Endosc. 2002;55:1-5.

Endoscopic Therapy

The chief methods of endoscopic Tx are: The chief methods of endoscopic Tx are: (1) thermal contact methods (heater probe, (1) thermal contact methods (heater probe,

multipolar electrocoagulation), in which the multipolar electrocoagulation), in which the bleeding vessel is compressed with a probe bleeding vessel is compressed with a probe

(2) injection of the bleeding site with dilute (2) injection of the bleeding site with dilute epinephrine/ saline/ ethanol…..epinephrine/ saline/ ethanol…..

(3) Endoclipping(3) Endoclipping

(4) Argon Plasma Coagulation (APC) (4) Argon Plasma Coagulation (APC)

Improving visualization

The efficacy of erythromycin was recently demonstrated in two RCT comparing erythromycin with no treatment or placebo.

Both studies showed that a single infusion of erythromycin (3 mg/kg given intravenously 20 or 60 to 120 minutes before endoscopy) significantly improved the quality of the endoscopic examination, resulting in a reduction of the need for second-look endoscopy

? Improvement of other outcomes? Improvement of other outcomes

Coffin et al. Gastrointest Endosc 2002;56:174–9.Frossard et al. Gastroenterology 2002;123:17–23.

Endoscopic Therapy

High-risk endoscopic stigmata (active bleeding or a visible vessel in an ulcer bed), 35% of pts is an indication for immediate endoscopic hemostatic

therapy A clot in an ulcer bed

warrants targeted irrigation in an attempt at dislodgment, with appropriate treatment of the underlying lesion

Low-risk endoscopic stigmata (a clean-based ulcer or a nonprotuberant pigmented dot in an ulcer bed) No need for endoscopic hemostatic therapy

Sacks et al, JAMA. 1990;264:494-9.Cook et al, Gastroenterology. 1992;102:139-48.

Endoscopic Therapy Primary hemostasis rates were 100% and 90% for

heater probe and injection therapy respectively vs. 8% in medically managed patients who presented with active ulcer bleeding.

Bardou and colleagues (meta-analyses of 56 studies) showed that, compared with drug or placebo treatment, endoscopic treatment was associated with statistically significant absolute decreases in rates of Re-bleeding, surgery, and mortality.

Gralnek et al. Gastrointest Endosc 1997;46(2):105-12.

Bardou M, Barkun A. [Abstract]. Gastroenterology. 2003;123:A239.Bardou M, Barkun A. [Abstract]. Gastroenterology. 2003;123:A625.

Injection therapy: which substance?

In individual trials, no statistically significant differences were seen for epinephrine alone versus distilled water, cyanoacrylate, epinephrine in combination with ethanolamine or

polidocanol, thrombin, sodium tetradecyl sulfate, or ethanol

Bardou M, Barkun A. [Abstract]. Gastroenterology. 2003;123:A239.

Injection vs thermo or electro-coagulation?

Most individual randomized studies have shown no differences in rates of re-bleeding, surgery, and mortality among coaptive therapy with heater probe thermocoagulation, multipolar electro-coagulation,

when compared with injection therapy

Chung et al, Gastroenterology. 1991;100:33-7.Lin et al, Gut. 1990;31:753-7.

Argon Plasma Coagulation (APC)?

in 185 patients with high-risk lesions, a randomized study, suggested no difference between injection plus heater probe and injection plus argon plasma coagulation

Chau et al, Gastrointest Endosc. 2003;57:455-61.

Monotherapy vs combination therapy

Combination treatment was associated with statistically significant reductions in absolute rates of re-bleeding compared with injection

alone, thermal treatment alone, or pharmacotherapy.

Similar reductions in re-bleeding were not observed when the combination was compared with hemoclip therapy alone, despite statistically significant reductions in surgery rates.

Bardou M, Barkun A. [Abstract]. Gastroenterology. 2003;123:A239.Jensen et al, Gastroenterology. 2002;123: 407-13.Lin et al, Gut. 1999;44:715-9.

The placement of clips

Endoscopic clips have shown superiority over heater probe or injection therapy in 2 trials but higher failure rates compared with injection therapy in another.

Studies of the combination of injection plus endoscopic clips have demonstrated no statistically significant benefit over injection alone or clips alone.

Cipolletta et al. Endoclips versus heater probe GI Endosc. 2001; 53:147-51.Gevers et al, Gastrointest Endosc. 2002;55:466-9.157

Is a second look necessary? A meta-analysis

Marmo et al. found that routine ‘second look’ endoscopy with retreatment as appropriate, significantly reduced the risk of recurrent bleeding, but did not substantially reduce the rates of surgery or mortality.

The absolute risk reduction in re-bleeding was 6.2% (P < 0.01).

Absolute risk reductions for surgery and mortality were, respectively, 1.7% and 1.0% (P=N.S.).

Thus, ‘second look’ endoscopy has failed to prove that it has an effect on key outcome parameters.

Marmo et al. Gastrointest Endosc 2003; 57: 62–7.Messmann et al, Endoscopy. 1998Chiu et al, GUT 2003

Re-bleeding: Endoscopic Re-treatment Vs Surgery

In the only randomized comparison, immediate endoscopic re-treatment in patients with re-bleeding after endoscopic hemostasis reduced the need for surgery without increasing the risk

for death and was associated with Fewer complications than surgery.

Lau et al. N Engl J Med. 1999;340:751-6.

LONG-TERM MANAGEMENT

There is unequivocal evidence supporting H. pylori eradication in patients with a peptic ulcer haemorrhage: treatment of infection decreases recurrent bleeding by 17% (NNT= 6) compared with acute ulcer healing treatment alone.

Most tests of active infection may exhibit increased false-negative rates in the context of acute bleeding.

Sharma et al, Aliment Pharmacol Ther. 2001;15:1939-47.Graham et al, Scand J Gastroenterol. 1993;28:939-42.Rokkas et al, Gastrointest Endosc. 1995;41:1-4.

Efficacy of diagnostic methods for H. pylori infection during upper gastrointestinal bleeding

Grino et al. Scand J Gastroenterol 2001; 36: 1254–8.

12 months after 12 months after treatmenttreatment

Leodolter et al. Aliment Pharma Ther 2001

Patient triage and disposition

Unsuccessful therapy

Surgery If cannot control the bleed Endoscopically or if re-bled for the 3rd time.

Therapeutic angiography is most strongly indicated in frail or severely ill patients who are poor surgical candidates.

Arterial embolization is generally safe in the UGI tract because of its rich arterial collateral supply.

Lefkovitz et al. Radiology in the diagnosis & therapy of GI bleeding. Gastroenterol Clin North Am 2000;29:489–512.

Surgeon problem is: Surgeon problem is: need enough cases to be well trainedneed enough cases to be well trained

CONCLUSIONS Non-variceal UGI bleeding is one of the most common

emergencies that internist & gastroenterologists encounter, and continues to be a significant cause of morbidity and mortality.

The keys to management are rapid resuscitation and stabilization; appropriate triage based on pre-endoscopic risk factors; early endoscopy to achieve prompt diagnosis and implement

hemostatic therapy to high-risk lesions; and aggressive antisecretory therapy (both oral & IV PPI) to reduce

the risk of continued or recurrent bleeding. Assessment of H. pylori status in all patients & eradication

therapy is currently accepted as a standard of care.