Post on 02-Jan-2016
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.