EBM in GI Emergency

1. EBM in GI Emergency Hsiu-Po Wang Department of Emergency Medicine National Taiwan University Hospital

2. EBM in GI emergency • Non-variceal UGI bleeding • Variceal UGI bleeding • Stress ulcer • Acute pancreatitis • Fulminant hepatic failure/ Hepatic coma

3. Consensus Recommendations for Nonvariceal Upper Gastroinestinal Bleeding Ann Intern Med. 2003;139:843-857

4. Categorizaion of Evidence

5. Recommendation • Immediate evaluation and appropriate resuscitation are critical to proper management • Evidence: III Opinions of respected authorties, based on clinical experience, descriptive studies, or reports of expert committees

6. Recommendation - NG tube • In selected patients, the placement of a NG tube can be considered because the findings may have prognostic value. • Evidence: II-3 Evidence obtained from comparisons between times or places with or without intervention, or dramatic results in uncontrolled experiments

7. Recommendation - NG tube • The detection of red blood with in-and-out NG: poor outcome and need for emergency endoscopy • RUGBE: the presence of bright blood in the aspirate was an independent predictor of rebleeding • OG or NG lavage may be helpful to clear the blood before endoscopy

8. Recommendation - Clinical stratification • Clinical stratification of patient into low- and high-risk categories is important for proper management. • Evidence: II-2 Evidence obtained from well-designed cohort or case-control studies, preferably from more than 1 center or research group

9. Recommendation - Clinical stratification • Rebleeding: > 65 years old, shock, poor overall health status, comorbid illnesses, low initial hb level, melena, transfusion requirement. fresh red blood on rectal examination/emesis/NG aspirate • Death: > 60 years old, shock, poor overall health status, comorbid illnesses, low initial Hb level, melena, transfusion requirement. fresh red blood on rectal examination/emesis/NG aspirate, inset of bleeding while hospitalized for another reason, sepsis, ↑ BUN/Cre/GOT • Specialty of attending physician influence the outcome

10. Recommendation - Early stratification based on clinical and endoscopic criteria • Early stratification of patient into low- and high-risk categories for rebleeding or mortality, based on clinical and endoscopic criteria, is important for proper management. • Evidence: I Evidence obtained from at least 1 properly randomized, controlled trial

11. Recommendation - Early stratification based on clinical and endoscopic criteria • Laine et al: clean ulcer base 5%, flat spot 10%, adherent clot 22%, nonbleeding visible vessel 43%, active bleeding 55% • Rockall risk score: age, shock, comorbidity, diagnosis, endoscopic stigmata of recent bleeding

12. Recommendation - disposition • Early endoscopy with risk classification by clinical and endoscopic criteria allows for safe and prompt discharge of patients classified as low risk • Evidence: I • Improves patient outcomes for patients classified as high risk • Evidence: II • And reduces resource utilization for patients classified as either low or high risk • Evidence: I

13. Recommendation –early endoscopy ? • Observation study: low-risk patients have no major complication in those triaged to outpatient care with early endoscopy • Retrospective cohort trial: hospital stay and need for surgery with early endoscopy in unselected patients↓ • Randomized, controlled trial: early endoscopy and endoscopic therapy ↓transfusion, hospital stay in patient with bloody NG aspirate • Patient at low risk, high risk, and unselected patients: ↓hosptial stay • Two randomized, controlled trial: Patient at low risk with early endoscopy43%~91% ↓ cost

14. Recommendation • NIH consensus(1989) and meta-analysis: benefits of endoscopic therapy mainly examined patients with high-risk • Meta-analysis(Bordou et al): endoscopic treatment ↓ rebleeding, surgery, and mortality, compared with drug or placebo • Endoscopic therapy for adherent clots ↓ rebleeding compared with medical therapy alone

15. Recommendation -second-look endoscopy • Routine second-look endoscopy is not recommended • Evidence: I • Second-look endoscopy may be of statistical benefit in select high-risk patients, but data are conflicting regarding its routine use • A second endoscopy is ultimately needed in patients whose initial endoscopic examination is incomplete

16. Recommendation - rebleeding • In cases of rebleeding, a second attempt at endoscopic therapy is generally recommended • Evidence: I • Randomized comparison: immediate endoscopic retreatment in patients with rebleeding after endoscopic hemostasis ↓need for surgery without increasing the risk for death and was associated with fewer complications

17. Recommendation - Surgical consultation • Surgical consultation should be sought for patients who have failed endoscopic therapy • Evidence: II-2 Evidence obtained from well-designed cohort or case-control studies, preferably from more than 1 center or research group • RUGBE: 14.1% rebleeding, 6.5% required surgery • Lau et al: 27% of high-risk patient with rebleeding after endoscopic treatment required salvage surgery

18. Recommendation - H2-receptor antagonists • H2-receptor antagonists are not recommended in the management of patients with acute UGI bleeding • Evidence: I Evidence obtained from at least 1 properly randomized, controlled trial

19. Recommendation - H2-receptor antagonists • H2-receptor antagonists are not recommended in the management of patients with acute UGI bleeding • Meta-analyses(Bardou et al): no significant improvement in outcomes compared with other pharmacotherpy or endoscopic therapy • PPI is more effective than H2-receptor antagonists and in preventing persistent or recurrent bleeding and surgery ( in selective patients )

20. Recommendation - non-variceal UGI bleeding • Somatostatin and octreotide are not recommended in the routine management of patients with acute non-varoceal UGI bleeding • Evidence: I • Meta-analyses: neither somatostatin nor octreotide improved outcomes compared with other endoscopic therapy or pharmacotherapy.

21. Recommendation - PPI • An iv bolus followed by continuous-infusion PPI is effective in decreasing rebleeding in patients who have undergone successful endoscopic therapy. • Evidence: I • Randomized trials: high dose bolus and continuous-infusion PPI have shown ↓rebleeding, ↓need forsurgery compared with H2 blocker or placebo • Meta-analyses: high dose PPI after successful endoscopic therapy ↓rebleeding • RUGBE: PPI ↓rebleeding, mortality in high-risk patient, trend toward ↓rebleeding in patient with low-risk.

22. Recommendation - PPI • In patient awaiting endoscopy, empirical therapy with a high-dose PPI should be considered. • Evidence III Opinions of respected authorties, based on clinical experience, descriptive studies, or reports of expert committees • Oral Losec reduce rebleeding with or without decreased rates of surgery • RUGBE: some efficacy in patients with both low- and high-risk endoscopic lesions

23. Recommendation - feeding • Patients considered at low risk for rebleeding after endoscopy can be fed within 24hours • Evidence: I • Randomized trial has shown that the time of rebleeding does not influence the hospital course of patients at low risk • Patient with major hemorrhage and endoscopic findings of a Mallory-Weiss tear or an ulcer with a clean base, flat spot, or clot may be fed and discharged home immediately after stabilization

24. At Patient Presentation • Immediately evaluate and initiate appropriate resuscitation • Consider placement of a NG tube in selected patients because the findings may have prognostic value • Stratify patients into low- and high-risk categories for rebleeding and death on the basis of clinical criteria. Use available prognostic scales to assist in decision making

25. At Endoscopy - I • Stratify patient into low- and high-risk categories for rebleeding and death on the basis of clinical and endoscopic criteria. Use available prognostic scales to assist in decision making. • Perform early diagnostic endoscopy (<24hrs) with risk classification by clinical and endoscopic criteria to assist in • Safe and prompt discharge of patients at low risk • Improvement of outcomes for patients at high risk • Reduction of resource utilization for patients at either low or high risk

26. At Endoscopy - II • Endoscopic hemostatic therapy is not indicated for patients with low-risk stigmata • Endoscopic hemostatic therapy is indicated for a patient with a clot in an ulcer bed, including targeted irrigation in an attempt at dislodgment, with appropriate treatment of the underlying lesion • Endoscopic hemostatic therapy is indicated for patients with high-risk stigmata.

27. Follow-up • Routine second-look endoscopy is not recommended • A second attempt at endoscopic therpay is generally recommended in cases of rebleeding • Seek surgical consultation for patients in whom endoscopic therapy has failed • Patients at low risk after endoscopy can be fed within 24 hours

28. Pharmacotherapy • H2-receptor antagonists are not recommended for patients with acute ulcer bleeding • Somatostatin and octreotide are not routinely recommended for patients with acute ulcer bleeding • IV bolus followed by continuous-infusion PPI can effectively decrease rebleeding in patients who have had successful endoscopic therapy • Consider high-dose PPI for patients awaiting endoscopy

29. EBM for treatment of variceal bleeding

30. Treatment of bleeding varices • Conservative treatment • Balloon tamponade • Somatostatin analogues • Terlipressin • Endoscopic ligation • Endoscopic sclerotherapy • Transjugular intrahepatic portosystemic shunt ( TIPS )

31. Somatostatin analogues for acute bleeding oesophageal varices • Treating bleeding oesophageal varices with somatostatin analogues does NOT appear to reduce deaths, but may lessen the need for blood transfusions The Cochrane Database of Systematic Reviews 2005 Issue 1

32. Terlipressin for acute esophageal variceal hemorrhage • 20 RCT included • A statistically significant reduction in mortality compared to placebo (relative risk 0.66, 95% confidence interval 0.49 to 0.88) • Terlipressin vssomatostatin or terlipressin vsendoscopic Txno statistically significant difference • Terlipressin vsballoon tamponade, terlipressin vsoctreotide, and terlipressin vsvasopressin ( small, low quality studies )  no difference in any of the major outcomes The Cochrane Database of Systematic Reviews 2005 Issue 1 (meta-analysis)

33. Terlipressin for acute esophageal variceal hemorrhage - Summary • Terlipressin appears to be as safe as other treatments • Terlipressin may reduce the mortality from variceal bleeding as compared to placebo • No sufficient data to decide whether terlipressin was better or worse than other available treatments such as other drugs (somatostatin, octreotide) or endoscopic Tx The Cochrane Database of Systematic Reviews 2005 Issue 1 (meta-analysis)

34. Endoscopic ligation vs pharmatherapy for acute bleeding oesophageal varices • Ligation is the most effective treatment option. • No significant difference was found between the efficacy of sclerotherapy and treatment with somatostatin or octreotide Endoscopy 2001;33(9): 737-46 (meta-analysis)

35. Sclerotherapy vs medical interventions for bleeding oesophageal varices in cirrhotic patients • No convincing evidence to support the use of emergency sclerotherapy for variceal bleeding in cirrhosis as the first, single treatment when compared with vasoactive drugs. The Cochrane Database of Systematic Reviews 2005 Issue 1

36. TIPS compared with endoscopic treatment for prevention of variceal rebleeding • Variceal rebleeding more frequent with ET (46.6%) than with TIPS (18.9%) • Post-treatment encephalopathy occurred significantly less often after ET (19%) than after TIPS (34%) • TIPS compared with ET reduces the rebleeding rate, but does not improve survival, and increasesthe incidence of encephalopathy in a period of 1 to 2.5 years Hepatology 1999;30(3):612-622 (meta-analysis )

37. Summary of Tx of bleeding varices • Treatment modalities are better than placebo • Endoscopic ligation may be the best option of treatment • Endoscopic sclerotherapy is not better than medications • Medications such as somatostatin, octreotide, terlipressin are safe in treatment of bleeding varices • No difference between somatostatin, octreotide, and terlipressin • TIPS ( compare with endoscopic Tx ) reduces rebleeding rate, but increases in the incidence of encephalopathy

38. EBM in GI emergency • Non-variceal UGI bleeding • Variceal UGI bleeding • Stress ulcer • Acute pancreatitis • Fulminant hepatic failure/ Hepatic coma

39. Opinions about stress ulcers • Stress ulcer bleeding is uncommon • Can occur in spite of prophylactic treatment • Should be considered as markers of prolonged survival in critically ill patients, rather than untreatable complications

40. Studies of stress ulcers More than 100 studies of the frequency, risk factors, and prophylaxis. These subjects continue to generate controversy. Why? Study methods, bleeding definition, patient population & number, and so on.

41. Cushing’s ulcer # associated with CNS injury # single deep lesion in the duodenum or stomach Curling’s ulcer # associated with thermal injury # may appear in the esophagus, stomach, small bowel & colon

42. Frequency of stress ulcer bleeding • Varies ( decrease recent years ) • Adult Before 1978, 5.3% - 33% 1978-1984 1.6% - 39% 1984-1994 0.1% - 39% ( average 6% ) • Pediatric population Clinical important bleeding: 20% in control group 5.7% in treated group

43. Coagulopathy platelet < 50000 mm3 PT > 2X control  Mechanical ventilation > 48 hours  History of GI ulcer or bleeding with one year At least 2 following risk factor: Sepsis ICU stay > 1 week Occult bleeding > 6 D High-dose corticsteriod >250mg/D Recommendation#1 (Adult )Prophylaxis for general ICU patients ASHP Therapeutic Guidelines

44. No definite conclusion : prophylaxis provides protection Risk factors: respiratory failrue coagulopathy Pediatric Risk of Mortality score > or /& = 10 Recommendation#1 (Pediatrics)Prophylaxis for general ICU patients Shock Surgery> 3 hr Trauma ASHP Therapeutic Guidelines

45. Recommendation#2 (Adult)Prophylaxis for special populations • Glasgow Coma Score < or/&= 10 • Thermal injury > 35% of BSA • Partial hepatectomy • Multiple trauma: Injury Severity Score > or/&=16 • Transplatation patients perioperatively • Hepatic failure • Spinal cord injuryASHP Therapeutic Guidelines

46. Recommendation#2 (Pediatrics)Prophylaxis for special populations • Thermal injury ( what BSA ?) • For other pediatric surgery or trauma, insufficient evidence to recommend prophylaxis. ASHP Therapeutic Guidelines

47. Recommendation#3 (Adult)Medications for prophylaxis • Conflicting results of meta-analyses & recent RCT • Choice among antacid, H2-antagonists, sucralfate: made on an institution-specific basis • Insufficient data on misoprostal or PPI ASHP Therapeutic Guidelines

48. Prophylactic agents for stress ulcer • Inhibition of gastric acid secretion H2 antagonist, PPI, prostaglandin analogue(?) • Neutralization of gastric acid anatacid • Protective mechanism sucralfate, misoprostol • HSP70 inducer (GGA), free-radical scavenger(?)

49. Prophylaxis for overt bleeding (I) Database of Abstracts of Reviews of Effects 2005 Issue 1 JAMA 1996;275(4):308-314 Sixty-three RCTs

50. Prophylaxis for overt bleeding (II) Database of Abstracts of Reviews of Effects 2005 Issue 1 JAMA 1996;275(4):308-314 Sixty-three RCTs