外科實證醫學課程

Somatostatin Analogues for Acute Bleeding Esophageal Varices

外科莊世昌 醫師

執行 EBM 的五個步驟 ( I )

1. 問問題（可以回答的問題）Converting the need for information into an

answerable question.

2.找資料（可獲得最好的證據資訊）Search the database and tracking down the

best evidence.

3.分析判斷（文獻的效度與重要性）Critical appraising that evidence for its

validity and importance.

執行 EBM 的五個步驟 ( II )

4. 臨床應用（整合三大層面） Integrating the critical appraising with our

clinical expertise and our patient’s unique biology, values and circumstances.

5.評估成果（執行 EBM的效率）Evaluating our effectiveness and efficiency

in executing step 1- 4 and seeking ways to improve them both for next time.

Case

王 xx 56 y/o male Hepatitis B Hx for 20+ years Liver cirrhosis since 3+ years UGI bleeding 2 episodes => Gastroendoscope: EV

bleeding Admission due to 3rd GI bleeding

Background Knowledge

Portal pressure (5-8mmHg)

1. Esophagogastric varices : coronary & short gastric v. to azygos v.

2. Caput medusae : epigastric v.

3. Retroperitoneal callateral vessels

4. Hemorrhoid venous plexus

5. Intrahepatic shunts

Portal Vein Physiology

Esophageal Varices

A. Noninterventional 1. Vasopressin, terlipressin 2. Somatostatin 3. Balloon tamponadeB. Interventionsal, nonsurgical 4. Endoscopic sclerotherapy 5. Endoscopic ligationC. Surgical 6. Emergency portasystemic shunts 7. Esophageal transection and reanastomosis 8. Esophagogastric devascularization 9. Suture ligation of varices

Treatment

Medications

1. Vasopressin ( 血管加壓素 )

2. Terlipressin

3. Somatostatin ( 體抑素 )

4. Octreotide

Octreotide

1. Sandostatin 0.1mg/1ml/Amp

2. Long-acting somatostatin analog 3. 降低奇靜脈血流4. 半衰期 : 90 min5. IV bolus 50-250 ug, continuous 50-250 ug/h6. Side effects: hyper or hypoglycemia, Abd. pain,

nausea, diarrhea, headache

Objectives

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

How to Ask Clinical Question You Can Answer?

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

問題以問題以 PICOPICO 形式呈現形式呈現

Patient / Problem

56 Y/O male liver cirrhosis with EV bleeding

Intervention Somatostatin Analogues

Comparison Intervention

Placebo

Outcome Decrease mortality , ……

搜 尋 技 巧 與 策 略資料庫的選擇關鍵字的設定

學習各種資料庫的搜尋方法圖書館定期開課

Step2 :Search Data for evidence

尋找文獻證據

醫學資料庫 網路資源

已經整理的文獻 未經整理的文獻

1.Cochrane Library2.EBMR 3.UptoDate 4.Clinical Evidence5. ACP J. club

1.Medline2.PubMed

常用實證醫學電子資源

Critical appraisal文獻的分析判斷

文獻的結果是否有可信度？ (Validity)

文獻的結果是否有重要性？ (Importance)

此資料如何運用於臨床工作 ?(Practice)

文獻的分析判斷前需先分類，不同種類的文獻，研究方法不同，評判方式也有異。最常見的四類文獻： Therapy, Harm, Diagnosis,

Prognosis

Step 3

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

Therapeutic study important

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

The Evidence Pyramid

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., <80% 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”

Seach Result

Cochrane 標誌及其意義Cochrane協作網標誌（見圖）由一個圓形圖以及圍繞圓形

圖的兩個粗體同心半環圖共同構成。1. 每一橫線代表一個試驗結果的可信區間，橫線越短則試

驗精度越高，結果越肯定2. 垂直線（代表 OR=1）將圓一分為二，可用於判斷結果

差別有無統計學意義，以區別治療效果，一般來說具有療效的試驗結果分佈於垂直線左側 ;若橫線落在垂直線右側 ,則表明治療結果無效。

3. 橫線與垂直線相接觸或相交，則表明該 RCT中的不同治療措施間差異無統計學意義。

4. 圓形圖內下方的菱形符號代表 7 個 RCT的綜合結果。符號位於左邊表明治療措施有效，位於右邊則表明治療措施弊大於利。

該圓形圖展示了一項短程價廉的激素類藥物Hydrocortisone治療可能早產的孕婦療

效的隨 機對照試驗系統評價結果。第一個試驗於 1972 年報導。至 1991 年，另外 6項試驗結果也相繼報導，但 7個試驗結果不一致，該療法是否利大於害，根據單個的臨床試驗結果難以確定。而系統評價結果明確肯定： Hydrocortisone的確可降低新生兒死於早產併發症的危險，使早產兒死亡率下降 30%-50% 。直至 1989 年，由於沒有進行相關的系統評價分析和報導，多數產科醫師並未認識到該項治療措施的效果 ,成千上萬的早產兒可能因其母親未接受相應治療而死亡（還耗費更多不必要的治療費用）。在臨床醫學中 ,由於未能根據RCTs製作出及時的、不斷更新的系統評價而導致以生命為代價的這類例子，不勝枚舉。

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 )

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.

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

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.

The trials were divided in two groupsHigh-quality group: the allocation of

patients to treatment groups had to be concealed and the trials had to be double-blind

Low-quality group

Types of Outcome Measures Mortality. Number of blood transfusions. Number with balloon tamponade. Number failing initial haemostasis. Number with rebleeding.

Results (1) The drugs did not reduce mortality

signicantlyRelative 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

Mortality

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.

Number of Transfusion

s

Results (3) Number of patients failing initial hemostasis was

reduced, relative risk 0.67 (0.53 to 0.86).

Number Failing Initial

Hemostasis

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,

Number With Rebleeding

Results (5) Use of balloon tamponade was rarely reported.

Number with Balloon Tamponade

Basic Calculations

Odds Ratio OR (a/b) / (c/d)

Relative Risk RR [a/(a+b)] / [c/(c+d)]

Relative Risk Reduction 1 – RR

Absolute Risk Reduction ARR [a/(a+b)] – [c/(c+d)]

Number Needed to Treat NNT 1 / ARR

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