將實證醫學納入臨床操作- 以Dextran之使用為例 徐圭璋 高雄榮民總醫院 kchsu@vghks.gov.tw

“Leaks” between research & practice Aware Accept Target Doable Recall Agree Done Valid Research 0.8 x 0.8 x 0.8 x 0.8 x 0.8 x 0.8 x 0.8 = 0.21 Prof. Paul Glasziou, EBM Centre, U. of Oxford, UK

實證醫學實作案例 顯微外科醫師為避免所接合的微小血管在術後阻塞，常用許多抗血栓劑。 Dextran 是常用的其中一種，卻又有嚴重併發症的可能， 如過敏性休克、急性腎衰竭、急性呼吸窘迫症候群等。 本科幾乎為常規使用。 基於其可怕併發症，使用之必要性令人懷疑，值得重新評估 。

實證醫學五步驟 提出問題 (Question formulation) 搜尋證據 (Evidence search) 嚴格判讀 (Critical appraisal) 恰當運用 (Evidence application) 評估結果 (Outcome evaluation)

實證醫學五步驟 提出問題 (Question formulation) 搜尋證據 (Evidence search) 嚴格判讀 (Critical appraisal) 恰當運用 (Evidence application) 評估結果 (Outcome evaluation)

Clinical Question (PICO) In patients with head and neck cancer, does use of dextran improve free flap survival rate? P (population): Pts with head neck cancer undergoing free flap surgery I (intervention): Dextran (or Rheomacrodex) C (control): none O (outcome): flap failure rate, morbidity OR mortality

實證醫學五步驟 搜尋證據 (Evidence search) 提出問題 (Question formulation) 嚴格判讀 (Critical appraisal) 恰當運用 (Evidence application) 評估結果 (Outcome evaluation)

Search terms & Strategy Databases: PubMed, MEDLINE & Cochrane Library Keywords: free flap, Dextran, Rheomacrodex Limitation: Randomized Controlled Trial

PubMed Dextran-related complications in head and neck microsurgery: do the benefits outweigh the risks? A prospective randomized analysis. Disa JJ, Polvora VP, Pusic AL, Singh B, Cordeiro PG. Plast Reconstr Surg. 2003 Nov;112(6):1534-9

MEDLINE Disa JJ. Polvora VP. Pusic AL. Singh B. Cordeiro PG. Dextran-related complications in head and neck microsurgery: do the benefits outweigh the risks? A prospective randomized analysis. [Clinical Trial. Journal Article. Randomized Controlled Trial] Plastic & Reconstructive Surgery. 112(6):1534-9, 2003 Nov.

Cochrane Library Dextran-related complications in head and neck microsurgery: do the benefits outweigh the risks? A prospective randomized analysis. Disa JJ, Polvora VP, Pusic AL, Singh B, Cordeiro PG Year: 2003

實證醫學五步驟 嚴格判讀 (Critical appraisal) 提出問題 (Question formulation) 搜尋證據 (Evidence search) 嚴格判讀 (Critical appraisal) 恰當運用 (Evidence application) 評估結果 (Outcome evaluation)

嚴格判讀 (Critical appraisal) 信度 效度 重要性 實際運用之可能

Systemic complications: The incidence of systemic (cardiac/pulmonary) complications is significantly greater in patients treated with low-molecular-weight dextran for 48 hours (p < 0.05) and 120 hours (p < 0.02) compared with patients treated with aspirin (ASA). (Disa JJ, Polvora VP, Pusic AL, Singh B, Cordeiro PG. Dextran-related complications in head and neck microsurgery: do the benefits outweigh the risks? A prospective randomized analysis. Plast Reconstr Surg. 2003 Nov;112(6):1534-9.)

Critical Appraisal Skills Programme (CASP) Screening Questions Y/N Comment Did the study ask a clearly focused question? 　 Consider if the question is ‘focused’ in terms of – the population studied – the intervention given – the outcomes considered Y Population right; Intervention right; Outcome: benefit/risk Was this a randomised controlled trial (RCT) and was it appropriately so? Consider: – why this study was carried out as an RCT – if this was the right research approach for the question being asked For such a therapy question, a systematic review is not available, a RCT is the right approach, and this is an RCT. Is it worth continuing?

Free Flap Survival in Literature. Source No, of cases Flap survival (%) Anticoagulation agent used Blackwell, 19992 119 99.2 Aspirin Jones wt al., 19963 305 91.2 LMWD and aspirin Simpson et al., 19964 150 95.0 Unknown Schusterman et al., 19945 308 94.5 Urken et al., 19946 200 93.5 LMWD Present study 216 97.2 Aspirin and SQH Chien et al. Aspirin and Low-Dose Heparin in Head and Neck Reconstruction. Laryngoscope. 2005 Jun;115(6):973-6.

400 free flaps for head and neck reconstruction Topical heparin irrigaton only during OP Aspirin 81 mg/day x 7 Only 3 complete flap losses Flap survival rate 99.2% JD Suh, JA Sercarz, E Abemayor et al Archives of Otolaryngology-Head & Neck Surgery 2004

Clinical Bottom Line Dextran對病患是有害的，如果功效不彰，不應使用。 所以不應使用。

實證醫學五步驟 恰當運用 (Evidence application) 提出問題 (Question formulation) 搜尋證據 (Evidence search) 嚴格判讀 (Critical appraisal) 恰當運用 (Evidence application) 評估結果 (Outcome evaluation)

想一下使用證據所需考慮的事

是否已考慮？ 研究文獻中的研究對象與臨床上實際面對的病患在本質上的差別 研究文獻中所運用的診斷或治療的方法所帶來的所有可能的好處與壞處 注意文獻中的納入及排除條件 研究文獻中所運用的診斷或治療的方法所帶來的所有可能的好處與壞處 是否已考慮其它替代方案 是否已考慮病患本身的價值觀

考量PESTELS (政經社科族法結) Political Economical Social Technological Ethnical Legal Structural

Factors to consider when applying evidence to individual patients Is the relative risk reduction that is attributed to the intervention likely to be different in this case because of the patient’s physiological or clinical characteristics? What is the patient’s absolute risk of an adverse event without the intervention? Is there significant comorbidity or a contraindication that might reduce the benefit? Are there social or cultural factors that might affect the suitability of treatment or its acceptability? What do the patient and the patient and the patient’s family want? BMJ 1998;317:139-42

指導實證醫學的三種模式 親身示範實證診療 運用實證醫學教導臨床醫學 指導特殊的實證醫學技能 學員將證據視為良好病患照護的一部份 示範指導 學員看著我們運用判斷力將證據應用到決策中 運用實證醫學教導臨床醫學 學員將證據視為良好臨床學習的一部份 將其他知識與實證交錯指導 學員看著我們運用判斷力將證據與其他知識結合 指導特殊的實證醫學技能 學員學習如何瞭解及運用證據 學員在學習過程中確實演練 學員看著我們運用判斷力執行實證醫學五步驟 實證醫學：臨床實踐與教學指引 陳杰峰 王慈蜂 2007

採用方法與結果 方法 結果 建立電子連絡網 準備工作 傳送該篇論文 引起注意 EBM簡介 概念溝通 論文評讀 實質討論 私下討論 動搖心理障礙 臨床示範 崩潰心防

實證醫學五步驟 評估結果 (Outcome evaluation) 提出問題 (Question formulation) 搜尋證據 (Evidence search) 嚴格判讀 (Critical appraisal) 恰當運用 (Evidence application) 評估結果 (Outcome evaluation)

評估結果 評估實證醫學本身各步驟的學習成效 醫療行為依照實證醫學而改變的成效評估 病人的醫療成果評估

結果 本科六位主治醫師於約一年內逐漸停用Dextran。 目前已全面停用約三年。 11/125 Dextran (-) vs 7/125 Dextran (+)

想一下該如何評估結果