A. ????????????

1
??????

• ??? ??

2
????????

• A. ????????????
• (Asking an answerable question)
• B. ??????
• (Tracking down the best evidence)
• C. ??????
• (Critical appraisal)
• D. ???????
• (Integrating the appraisal with clinical
  expertise patients' preference)
• E. ????????
• (Auditing performance in step 1-4)

(???? ??????????? ???,??? 2004)
3
EBM worksheet

1. Clinical scenario
2. Background knowledge
3. Question by PICO
4. Search strategy
5. Search outcome
6. Citations
7. Evidence appraisal
8. Conclusion
9. Plain-language explanation

Step A
Step B
Step C
Step D
4
?????????

• ?????????????????
• ????????
• ???/???
• (Patient)
• ??(???)
• (Intervention)
• ??,??????
• (Comparison)
• ????,???????????
• (Outcome)

PICO
(???? ????????? Sharon E. Straus??? ???,?????
2007 )
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1. Clinical scenario

• ???,45???,????????,????????????????????,????????
  ?diluted epinephrine,?????????(PPI)??,??????????1?
  ,2?,5?

6
2.Background knowledge

• ?? ????
• Forrest I Active bleeding
• Ia Active pulsation 90
• Ib Active oozing 30
• Forrest II Bleeding stigmata
• IIa Visible vessel 50
• IIb Clot 20
• IIc Black base lt5
• Forrest III No bleeding signs
• Clear ulcer base lt5

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Role of acid in haemostasis

• Impairs clot formation
• Impairs platelet aggregation and causes
• disaggregation
• Accelerates clot lysis
• Predominantly acid-stimulated pepsin
• May impair integrity of mucus/bicarbonate barrier
• gt??PH??!!

8
pH Matters

• Intragastric pHgt3 Correlated with DU healing1
• Intragastric pHgt4 Correlated with healing of
  gastric
• ulcer2
  erosive esophagits3
• Intragastric pHgt6 Correlated with clot formation
  4,5
• prevention of
  ulcer rebleeding
• 1Johnes DB et al. Gut 1987 281120-7
• 2Bell NJV et al. Digestion 1992 51(suppl 1)
  59-67
• 3Howden CW et al. Aliment Pharmacol Ther 1990
  425-33
• 4Green FJ et al. Gastroenterology 1978
  7438-43
• 5Patchett SE et al. Gut 1989 301704-7

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Bolus Followed by Bolus
Julapalli V et al. Dig Dis Sci 2005 501185-93
10
Median pH profiles in eight healthy subjects
after receiving anintravenous infusion of 80 mg
of pantoprazole followed by 8 mg/hr asa constant
infusion
5vials qd
Julapalli V et al. Dig Dis Sci 2005 501185-93
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3. Question by PICO

• P (Patient)
• ???,45???,????????,????
• ????????????????
• I (Intervention)
• Pantoprazole ( 40mg/vial) 2 or 5 vials qd
• Bolus or constant infusion
• C (Comparison)
• 1 vial qd, iv bolus
• O (Outcome) ?????,????????

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4. Search strategy-1

• Search Cochrane Database Syst Rev for ulcer
  bleeding and proton-pump inhibitor
• ? One review article found, but irrelevant

13
4. Search strategy-2

• Search PubMed for ulcer bleeding and proton-pump
  inhibitor
• -- 390 papers found
• Limits English,human,meta-analysis,RCT
• -- 52 papers found
• Limits English,human,meta-analysis,
• -- 19 papers found

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15
??Oxford Center??????
Level Therapy/Prevention, Aetilogy/Harm
1 a ?????????(Randomized Clinical Trial, RCT)??????(systemic review, SR)?????
b ????????????RCT???
c ??????????,??????????????????????(all or none)??????
2 a ?????????(cohort studies)??????????
b ??????????????RCT???
c ???????????,???????("Outcomes" research ecological studies)?
3 a ??????????(case control studies)???????????
b ?????????(individual case control study)?
4 ??????,???????????????
5 ?????????,?????????????????????
(Produced by Bob Phillips, Chris Ball, Dave
Sackett, Doug Badenoch, Sharon Straus, Brian
Haynes, Martin Dawes since November 1998)
16
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17
(No Transcript)
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6. Citations

• Meta-analysis proton-pump inhibition in
  high-risk patients with acute peptic ulcer
  bleeding.
• Aliment Pharmacol Ther. 2005 Mar 1521(6)677-86
  
• METHODS MEDLINE was used to identify randomized
  trials (01/1990-04/2003) that assessed the
  efficacy of pharmacological treatments for
  patients with bleeding peptic ulcers exhibiting
  high-risk stigmata (Forrest Ia-IIb). Three groups
  of treatment were assessed proton-pump
  inhibitors given as
• ? high-dose bolus followed by intravenous
  constant infusion
• ? ? ? ? ? (40-80 mg and at least 6 mg/h),
• ? high-dose oral proton-pump inhibitors
• ? ? ? ? ? (at least twice the standard dosage),
• ? non-high-dose proton-pump inhibitors
• ? ? ? ? ? (other proton-pump inhibitors dosing
  schedules)
• ? Mixed-effect models were used to determine rate
  differences between treatment and control groups.

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Non-high-dose proton-pump inhibitor regimens

• 2040 mg bolus every 36 h
• 40 mg bolus followed by 80 mg/day continuous
  infusion
• 40 mg q12 h for 3 days
• 80 mg bolus followed by 40 mg q12 
• 40 mg q12 h for 2 days followed by 40 mg/day oral

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• Results
• -- high-dose bolus followed by intravenous
  constant infusion
• gtsignificantly decreases ulcer rebleeding,
  surgery and mortality
• -- high-dose oral proton-pump inhibitors
• gt reduced rebleeding but not surgery or
  mortality
• -- non-high-dose proton-pump inhibitors
• gtreduced rebleeding, surgery and mortality

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8. Conclusion

• PPIs (vs. placebo)
• intravenous 80 mg bolus and then 8 mg/h
• ?????????PH?gt6,????????,??????,??????
• ?????PPIs?????
• ? 40mg qd or bid vs. high-dose ??

23
Appropriate use of intravenous proton pump
inhibitors in the management of bleeding peptic
ulcer
Julapalli V et al. Dig Dis Sci 2005 501185-93
24
9. Plain-language explanation

• ??????????????,?????????????????? Pantoprazole (
  40mg/vial) intravenous 80 mg bolus and then 8mg/h
• ??40mg qd or bid ????????????

25
Policy or practice change

• 1 amp qd iv?????,?????
• ???

26
???? !!
27
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6. Citations

• Low-dose intravenous pantoprazole for optimal
  inhibition of gastric acid in Korean patients.
• J Gastroenterol Hepatol. 2007 Sep22(9)1429-34
• BACKGROUND AND AIM Proton-pump inhibitor (PPI)
  therapy for bleeding ulcers is more efficacious
  in Asian patients than in non-Asian patients. The
  aim of this study was to evaluate the efficacy of
  various doses of pantoprazole on intragastric
  acidity in Korean patients. METHODS A
  prospective randomized study was conducted in 52
  patients either with bleeding peptic ulcers after
  successful endotherapy or who received endoscopic
  mucosal resection for gastric neoplasms. Patients
  were randomized into two doses of intravenous
  pantoprazole 40 mg q.d. and 40 mg b.i.d. We
  compared these results with our preliminary study
  utilizing high-dose pantoprazole (80 mg 8
  mg/h). The potential contribution of CYP2C19
  genetic polymorphisms and the presence of
  Helicobacter pylori were also assessed. RESULTS
  Pantoprazole 40 mg b.i.d. and high-dose
  pantoprazole demonstrated better inhibition of
  intragastric acid than pantoprazole q.d. (P lt
  0.05). The pantoprazole 40 mg q.d. group
  exhibited significant variations in acid
  inhibition correlating with CYP2C19 genotype.
  Median 24 h pH values did not differ
  significantly between the pantoprazole b.i.d. and
  high-dose pantoprazole groups, regardless of H.
  pylori infection status. A median intragastric pH
  lt 6.0 was observed in only three of 28 patients
  in the 40 mg b.i.d. group these three patients
  were extensive metabolizers.
• CONCLUSION A 40 mg b.i.d. dose of pantoprazole
  is sufficient to maintain pH gt 6.0 in Korean
  patients, except for patients with extensive
  metabolizing CYP2C19 genotypes.