花花牛奶

作者：Laurie Barclay, MD  
出處：WebMD醫學新聞

　　May 11, 2010 — 根據一項5月10日發表於內科學誌的收納隨機分派研究系統性綜論與綜合分析結果，在治療出血性消化性潰瘍方面，高劑量質子幫浦阻斷劑(PPIs)可能沒有比低劑量更好。這一系列與質子幫浦阻斷劑有關的文章，以「少即是多（less is more）」的標題發表在內科學誌上。
　　
　　台灣大學醫學院附設醫院的Chih-Hung Wang醫師與其同事們寫到，高劑量PPIs（80-mg靜脈推注，之後以8-mg/h持續輸注72小時）的用法已經被廣泛研究且使用。然而，目前並沒有具體的證據證實高劑量PPIs類藥物比非高劑量PPIs類藥物有效。
　　
　　研究者們搜尋比較高劑量PPIs類藥物相較於非高劑量PPIs類藥物用於出血性消化性潰瘍患者再出血、需手術介入以及死亡率的隨機分派研究文獻。綜合分析收納7項高品質隨機分派研究，共1157位患者，合併預後數據，並以勝算比（OR）報告結果。
　　
　　相較於非高劑量PPIs類藥物，高劑量PPIs類藥物在再出血機率（7項研究共1157位患者；OR為1.30；95%信賴區間[CI]為0.88-1.91）、需手術介入（6項研究共1052位患者；OR為1.49；95% CI為0.66-3.37）、死亡率（6項研究共1052位患者；OR為0.98；95% CI為0.37-2.13），統計上並無顯著差異。根據事後次組分析，起始內視鏡時，最近出血的病徵嚴重度、使用PPIs類藥物途徑、或是PPIs類藥物劑量並未改變綜合起來的結果。
　　
　　試驗作者寫到，相較於非高劑量PPIs類藥物，高劑量PPIs類藥物並未進一步降低罹患出血消化性潰瘍患者內視鏡治療後再出血機率、需外科介入以及死亡率。
　　
　　這項研究的限制包括未能以意向分析原則產出數據；沒有以隧道圖偵測發表誤差；以及僅收納7項研究，大部份收納病患並不多。
　　
　　【主編評論：考慮其他治療】
　　在隨後的主編評論中，來自加州舊金山公共衛生部門Mitchell H. Katz醫師描述這項系統性綜論以及該系列其他研究是「少即是多」。
　　
　　Katz醫師寫到，對大部份病患而言，使用PPIs類藥物壞處多過於好處。降低不必要地使用這些藥物需要醫師與病患的行動。身為醫師，我們應該提供其他治療功能性消化不良、處方短期PPIs類藥物治療（在討論可能的風險與好處後），並且考慮對無症狀患者停止使用PPIs類藥物治療。
　　
　　試驗作者們表示沒有相關資金上的往來。
　　
　　Katz醫師是健康處理協會（Health Management Associates）的獨立諮詢專家。


High-Dose Proton Pump Inhibitors May Be No More Effective Than Lower Doses for Bleeding Peptic Ulcer

By Laurie Barclay, MD
Medscape Medical News

May 11, 2010 — High-dose proton pump inhibitors (PPIs) may be no more effective than lower doses for bleeding peptic ulcer, according to the results of a systematic review reported in the May 10 issue of the Archives of Internal Medicine. The article describing this systematic review and meta-analysis of randomized controlled trials is part of a series about PPIs published in the Archives of Internal Medicine entitled "Less Is More."

"High-dose...PPIs (80-mg bolus, followed by 8-mg/h continuous infusion for 72 hours) have been widely studied and used," write Chih-Hung Wang, MD, from National Taiwan University Hospital and National Taiwan University College of Medicine in Taipei, and colleagues. "However, to date no concrete evidence has shown that high-dose PPIs are more effective than non–high-dose PPIs."

The reviewers searched the literature for randomized controlled trials comparing rebleeding, surgical intervention, and mortality seen with the use of high-dose PPIs vs non–high-dose PPIs in patients with bleeding peptic ulcer. A meta-analysis of 1157 patients from 7 high-quality randomized studies combined outcomes data, which were reported as odds ratios (ORs).

Compared with non–high-dose PPIs, high-dose PPIs had statistically similar effects on rates of rebleeding (7 studies enrolling a total of 1157 patients; OR, 1.30; 95% confidence interval [CI], 0.88 - 1.91), surgical intervention (6 studies enrolling a total of 1052 patients; OR, 1.49; 95% CI, 0.66 - 3.37), and mortality (6 studies enrolling a total of 1052 patients; OR, 0.89; 95% CI, 0.37 - 2.13). Severity of signs of recent hemorrhage at initial endoscopy, route of PPI administration, or PPI dose did not affect summary outcome measures, according to the results of post hoc subgroup analyses.

"Compared with non–high-dose PPIs, high-dose PPIs do not further reduce the rates of rebleeding, surgical intervention, or mortality after endoscopic treatment in patients with bleeding peptic ulcer," the study authors write.

Limitations of this study include failure to use the intent-to-treat principle for data synthesis; lack of funnel plots to detect publication biases; and inclusion of only 7 studies, most of which enrolled few patients.

Editorial: Consider Other Treatments

In an accompanying editorial, Mitchell H. Katz, MD, from the San Francisco Department of Public Health, San Francisco, California, describes this systematic review as well as the other studies described in the series, "Less Is More."

"For most patients the adverse effects of PPIs outweigh the benefits," Dr. Katz writes. "Reducing the unnecessary use of these medications will require action by both physicians and patients. As physicians, we should offer treatments other than PPIs for functional dyspepsia, prescribe short courses of PPI treatment (after disclosure of possible risks and benefits), and consider a trial of discontinuing PPI therapy in patients who are asymptomatic."

The study authors have disclosed no relevant financial relationships.

Dr Katz is an independent consultant for Health Management Associates.

Arch Intern Med. 2010;170:747-748, 751-758.