Somatostatin Analogues for Acute Bleeding Esophageal Varices

1
????????

• Somatostatin Analogues for Acute Bleeding
  Esophageal Varices

?? ??? ??
2
??EBM????? ( I )

• 1.???(???????)
• Converting the need for information into an
  answerable question.
• 2.???(??????????)
• Search the database and tracking down the best
  evidence.
• 3.????(?????????)
• Critical appraising that evidence for its
  validity and importance.

3
??EBM????? ( II )

• 4.????(??????)
• Integrating the critical appraising with our
  clinical expertise and our patients unique
  biology, values and circumstances.
• 5.????(??EBM???)
• Evaluating our effectiveness and efficiency in
  executing step 1- 4 and seeking ways to improve
  them both for next time.

4
Case

• ?xx 56 y/o male
• Hepatitis B Hx for 20 years
• Liver cirrhosis since 3 years
• UGI bleeding 2 episodes gt Gastroendoscope EV
  bleeding
• Admission due to 3rd GI bleeding

5
Background Knowledge
6
(No Transcript)
7
Portal Vein Physiology

• Portal pressure (5-8mmHg)
• Esophagogastric varices coronary short
  gastric v. to azygos v.
• Caput medusae epigastric v.
• Retroperitoneal callateral vessels
• Hemorrhoid venous plexus
• Intrahepatic shunts

8
Esophageal Varices
9
Treatment
A. Noninterventional 1. Vasopressin,
terlipressin 2. Somatostatin 3.
Balloon tamponade B. Interventionsal,
nonsurgical 4. Endoscopic sclerotherapy
5. Endoscopic ligation C. Surgical 6.
Emergency portasystemic shunts 7.
Esophageal transection and reanastomosis
8. Esophagogastric devascularization 9.
Suture ligation of varices
10
Medications

1. Vasopressin (?????)
2. Terlipressin
3. Somatostatin (???)
4. Octreotide

11
Octreotide

1. Sandostatin 0.1mg/1ml/Amp
2. Long-acting somatostatin analog
3. ???????
4. ??? 90 min
5. IV bolus 50-250 ug, continuous 50-250 ug/h
6. Side effects hyper or hypoglycemia, Abd. pain,
   nausea, diarrhea, headache

12
Objectives

• To study whether somatostatin or analogues
  improve survival or reduce the need for blood
  transfusions in patients with bleeding
  oesophageal varices.

13
How to Ask Clinical Question You Can Answer?
14
???PICO????
Patient or Problem Intervention Comparison Intervention Outcome
Description of the patient or the target disorder of interest Could include Exposure Diagnostic test Prognostic factor Therapy Patient perception etc. Relevant most often when looking at therapy questions Clinical outcome of interest to you and your patient
15
Patient / Problem 56 Y/O male liver cirrhosis with EV bleeding
Intervention Somatostatin Analogues
Comparison Intervention Placebo
Outcome Decrease mortality ,
16
? ? ? ? ? ? ?
Step2 Search Data for evidence

• ??????
• ??????
• ????????????
• ???????

17
??????????
18
(No Transcript)
19
(No Transcript)
20
(No Transcript)
21
(No Transcript)
22
(No Transcript)
23
(No Transcript)
24
Critical appraisal???????
Step 3

• ???????????? (Validity)
• ???????????? (Importance)
• ?????????????(Practice)
• ????????????,???????,??????,????????
• ????????Therapy, Harm, Diagnosis, Prognosis

25
Diagnostic study important

• Sensitivity
• Specificity
• Likelihood ratio for a positive test result
• Likelihood ratio for a negative test result
• Positive predictive value
• Negative predictive value
• Pre-test probability (prevalence)
• Pre-test odds prevalence/(1-prevalence)
• Post-test odds pre-test odds ? LR

26
Therapeutic study important

• Control event rate (CER)
• Experimental event rate (EER)
• Relative risk reduction (RRR)
• Absolute risk reduction (ARR)
• Number needed to treat (NNT)

27
The Evidence Pyramid
28
Levels of Evidence and Grades of Recommendations
Grade of Recommendation Level of Evidence Therapy/Prevention, Aetiology/Harm Prognosis
A 1a SR (with homogeneity) of RCT SR (with homogeneity) of inception studies, or a CPG validated on a test set
A 1b Individual RCT (with narrow Confidence Interval) Individual inception cohort study with ?80 follow-up
A 1c All or none All or none case-series
B 2a SR (with homogeneity) of cohort study SR (with homogeneity) of either retrospective cohort studies or untreated control groups in RCTs
B 2b Individual cohort study (include low quality RCT e.g., lt80 follow-up) Retrospective cohort study or follow-up untreated control patients in an RCT or CPG not validated in a test set.
B 2c Outcomes Research Outcomes Research
B 3a SR (with homogeneity) of case-control studies
B 3b Individual Case-Control Study
C 4 Case-series (and poor quality cohort and case-control studies) Case-series (and poor quality prognostic cohort studies)
D 5 Expert opinion without explicit critical appraisal, or based on physiology bench research or first principles Expert opinion without explicit critical appraisal, or based on physiology bench research or first principles
29
Seach Result
30
(No Transcript)
31
Cochrane??????

• Cochrane?????(??)????????????????????????????
• ?????????????????,???????????,?????
• ???(??OR1)??????,????????????????,???????,???????
  ????????????????????????,??????????
• ????????????,????RCT??????????????????
• ?????????????7?RCT????????????????????,???????????
  ?????

32

• ??????????????????? Hydrocortisone????????????
  ? ??????????????????1972 ?????1991?,??6?????????
  ?,?7????????,?????????,???????????????????????????
  Hydrocortisone??????????????????,?????????30-50
  ???1989?,??????????????????,????????????????????,?
  ???????????????????????(?????????????)???????,????
  ??RCTs??????????????????????????????,?????

33
Seach Strategy

• MEDLINE (PubMed) from 1966 to Feb 2004
• Key word (somatostatin or octreotide or
  vapreotide or lanreotide) combined with (varic
  or bleed or hemorrhag or hematemesis or melena)
• The Cochrane library
• Key word (somatostatin explode all trees (mesh)
  or somatostatin or octreotide or vapreotide or
  lanreotide) and (varic or bleed or hemorrhag
  or hematemesis or melena )

34
Selection Criteria

• All randomised trials comparing somatostatin or
  analogues with placebo or no treatment in
  patients suspected of acute or recent bleeding
  from oesophageal varices.

35
Description of Studies

• Included 20 trials (2518 patients, average of
  about 100 patients per trial)
• The dose schedules and length of treatment were
  quite variable

36
Methodological Quality

• Double-blind nine trials
• Blinding during data analysis four trials
• All or nearly all (90) of the randomised
  patients in the analysis seven trials
• In four trials, some of the randomised patients
  were excluded because the source of bleeding was
  judged to be non-variceal
• In the remaining trials it was not clear whether
  there had been additional patients that were not
  accounted for.

37
(No Transcript)
38

• The trials were divided in two groups
• High-quality group the allocation of patients to
  treatment groups had to be concealed and the
  trials had to be double-blind
• Low-quality group

39
Types of Outcome Measures

• Mortality.
• Number of blood transfusions.
• Number with balloon tamponade.
• Number failing initial haemostasis.
• Number with rebleeding.

40
Results (1)

• The drugs did not reduce mortality signicantly
• Relative risk 0.96 (95 condence interval (CI)
  0.74 to 1.24) for the high-quality trials
• 0.79 (95 CI 0.61 to 1.02) for other trials

41
Mortality
42
Results (2)

• Units of blood transfused
• Relative risk 0.7 (0.3 to 1.2) less with drugs
  in the high-quality trials
• 1.5 (0.9 to 2.0) less in the low-quality trials.

43
Number of Transfusions
44
Results (3)

• Number of patients failing initial hemostasis was
  reduced, relative risk 0.67 (0.53 to 0.86).

45
Number Failing Initial Hemostasis
46
Results (4)

• Rebleeding was not signicantly reduced
• Relative risk 0.82 (0.45 to 1.49) in the
  high-quality trials
• Relative risk 0.35 (0.18 to 0.67) in the
  low-quality trials,

47
Number With Rebleeding
48
Results (5)

• Use of balloon tamponade was rarely reported.

49
Number with Balloon Tamponade
50
(No Transcript)
51
Basic Calculations
Odds Ratio OR (a/b) / (c/d)
Relative Risk RR a/(ab) / c/(cd)
Relative Risk Reduction 1 RR
Absolute Risk Reduction ARR a/(ab) c/(cd)
Number Needed to Treat NNT 1 / ARR
52
Q A ?????????!