抗血栓藥物在內(nèi)鏡操作時的管理.docVIP

Management【管理】 of antithrombotic 【抗血栓形成的】agents 【藥劑】for endoscopic【內(nèi)窺鏡檢查的】 procedures【程序、操作、步驟、過程】 This is one of a series of statements discussing the use of GI endoscopy 【胃腸內(nèi)鏡檢查】in common clinical situations. The Standards【標準】 of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE)【美國胃腸鏡協(xié)會】 prepared this text. This guideline【指導(dǎo)原則】 combines and updates 2 previously【以前】 issued guidelines, Guideline on the management of antithrombotic and antiplatelet therapy 【抗血小板治療】for endoscopic procedures1 and ASGE guideline: the management of low-molecular-weight heparin【低分子肝素】 and nonaspirin【非阿司匹林】 antiplatelet agents for endoscopic procedures.2 To prepare this guideline, a search of the medical literature was performed using PubMed【免費搜索引擎，提供生物醫(yī)學(xué)方面的論文搜索以及摘要】. Studies or reports that described fewer than【少于】 10 patients were excluded from analysis if multiple series with more than 10 patients addressing the same issue were available. Additional【額外的】 references【參考】 were obtained【獲得】 from the bibliographies【文獻】 of the identified【確認】 articles and from recommendations【推薦、建議】 of expert consultants【專家顧問】. Guidelines for appropriate【合適的】 use of endoscopy are based on a critical review【批評性審查】 of the available data and expert consensus【一致同意】 at the time the guidelines are drafted【制定、起草】. Further controlled clinical studies may be needed to clarify【使清楚，澄清】 aspects【方面】 of this guideline. This guideline may be revised【修訂、修正】 as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations【推薦、建議】 are based on reviewed studies【綜述研究】 and were graded on【被分級】 the strength of the supporting evidence (Table 1).3 The strength of individual【個人的、獨特的】 recommendations is based on both the aggregate【總數(shù)的、總計的】 evidence quality and an assessment【評估、評價】 of the anticipated【預(yù)先的、預(yù)期的】 benefits and harms. Weaker【微弱的、無說服力的】 recommendations are indicated by phrases such as “we suggest” whereas stronger recommendations are typically stated as “we recommend.”TABLE 1. GRADE system for rating the quality of evidence for guidelinesQuality of evidence Definition【定義】 SymbolHigh qualityFurther research is very unlikely to change our confidence in the estimate of effect+Moderate qualityFurther research is likely tohave an important impact onour confidence in the estimateof effect and may change theestimate+-Low qualityFurther research is very likelyto have an important impacton our confidence in the estimateof effect and is likely to changethe estimate+-Very low qualityAny estimate of effect is veryuncertain +-Weaker recommendations are indicated by phrases such as we suggest, whereas stronger recommendations are typically stated as we recommend.Adapted from Guyatt et al.3 This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patients condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from this guideline. Antithrombotic agents include anticoagulants【抗凝劑】 (eg, warfarin, heparin, and low molecular weight heparin) and antiplatelet【抗血小板的】 agents (eg, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), thienopyridines【噻吩并吡啶】 (eg, clopidrogrel【氯吡格雷】 and ticlopidine【噻氯吡啶】), and glycoprotein IIb/IIIa receptor inhibitors【糖蛋白IIb/IIIa受體抑制劑】). Antithrombotic therapy【治療】 is used to reduce the risk of thromboembolic events【血栓栓塞事件】 in patients with certain【某一，必然的】 cardiovascular【心血管的】 conditions (eg, atrial fibrillation【心房纖顫】 and acute coronary syndrome【ACS急性冠脈綜合征】), deep venous thrombosis (DVT)【深部靜脈血栓形成】, hypercoagulable states【高凝狀態(tài)】, and endoprostheses【內(nèi)鏡置管術(shù)】. The most common site of significant bleeding in patients receiving oral anticoagulation therapy【口服抗凝治療】 is the GI tract【胃腸道】.4 The antithrombotic drug classes with【把.與.歸入一類】 duration of action and routes for reversal【逆轉(zhuǎn)】 are described in Table 2.TABLE 2. Antithrombotic drugs: duration of action and routes for reversalRoutes for reversalDrug classSpecific agent(s)Duration【持續(xù)的時間，持續(xù)】 of actionElective【可選擇的】Urgent 【極力主張的，急迫的】AntiplateletagentsAspirin10 days NATransfuse platelets【血小板輸注】NSAIDsVaries 【相應(yīng)變化】NATransfuse plateletsDipyridamole【雙嘧達莫】2-3 daysHoldTransfuse plateletsThienopyridines (clopidrogrel,【氯吡格雷】 ticlopidine【】噻氯吡啶)3-7 daysNATransfuse platelets desmopressin【去氨加壓素】 if overdoseGP IIb/IIIa inhibitors (tirofiban, abciximab, eptifibatide)VariesNATransfuse platelets; in case of overdose, some agents can be removed with dialysis【透析】AnticoagulantsWarfarin3-5 daysHoldFFP vitamin K, consider protamine sulfate*Unfractionated heparin【未分離肝素】4-6 hHoldHold or consider protamine sulfate*LMWH【低分子肝素】12-24 h HoldHold or consider protamine sulfate【硫酸魚精蛋白】*NA, Not applicable; NSAID, nonsteroidal anti-inflammatory drug; GP, glycoprotein; FFP, fresh frozen plasma; LMWH, low molecular weight heparin.*Caution: Can cause severe hypotension and anaphylaxis. Before performing（【執(zhí)行】 endoscopic【內(nèi)鏡檢查】 procedures on patients taking antithrombotic medications, one should consider the urgency【緊迫，緊要】 of the procedure and the risks of (1) bleeding related solely【唯一地，僅僅】 to antithrombotic therapy, (2) bleeding related to an endoscopic intervention performed in the setting of antithrombotic medication use, and (3) a thromboembolic event related to interruption of antithrombotic therapy. Alternative【備選的，替代的，其他的】 diagnostic【診斷的】 studies for patient evaluation【診斷（醫(yī)學(xué)）；估價】 (eg, video capsule endoscopy【膠囊內(nèi)鏡】 or radiologic studies【放射檢查】) should also be considered as well as the use of resources for hospitalization【住院治療】, parenteral【胃腸外的】 antithrombotic therapy, and laboratory tests【實驗室檢查】 used to monitor【監(jiān)測，記錄】 antithrombotic therapy.Furthermore, potential【潛在的】 thromboembolic events that may occur with withdrawal【撤回，撤退】 of medication can be devastating【可怕的，毀滅性的】,whereas【鑒于】 bleeding after high-risk procedures, although increased in frequency【頻繁性】, is rarely【罕有的】 associated with any significant morbidity【發(fā)病率，病態(tài)】 or mortality【死亡率，死亡數(shù)】. Discussion with the patient and his or her prescribing physician【處方醫(yī)生】 before the procedure is invaluable【無法估計】 to help determine whether antithrombotic agents should be stopped or adjusted【調(diào)整】 in any particular patient. This guideline is an update of two previous ASGE guidelines1,2 and addresses the management of patients undergoing【經(jīng)歷，承受】 endoscopic procedures who are receiving antithrombotic therapy, providing recommendations and management【管理】 algorithms【運算法則】.DEFINITIONS【定義，規(guī)定】Procedure risks【操作風(fēng)險】 Endoscopic procedures vary in their potential to produce significant or uncontrolled bleeding (Table 3).Low-risk procedures include all diagnostic procedures including those with mucosal biopsy【粘膜活檢】5,6 and ERCP【內(nèi)鏡逆行胰膽管造影】 without sphincterotomy【括約肌切開術(shù)】,7,8 diagnostic balloon-assisted enteroscopy【氣囊輔助內(nèi)鏡檢查】,9 and EUS 【超聲內(nèi)鏡】without FNA 【細針抽吸】or Tru-Cut needle biopsy.10TABLE 3. Procedure risk for bleedingHigher-risk procedures Low-risk proceduresPolypectomy Diagnostic (EGD, colonoscopy, flexible sigmoidoscopy)Biliary or pancreatic sphincterotomy including biopsy Pneumatic or bougie dilation ERCP without sphincterotomy EUS without FNAPEG placement Enteroscopy and diagnostic balloon-assisted enteroscopyTherapeutic balloon-assisted enteroscopy Capsule endoscopy Enteral stent deployment (without dilation) EUS with FNA Endoscopic hemostasisTumor ablation by any techniqueCystogastrostomyTreatment of varices Higher-risk procedures include those associated with an increased risk of bleeding, such as endoscopic polypectomy【內(nèi)鏡息肉切除術(shù)】,11,12 therapeutic balloon-assisted enteroscopy,9,13 endoscopic sphincterotomy【內(nèi)鏡下括約肌切開術(shù)】,14 and those procedures with the potential to produce bleeding that is inaccessible or uncontrollable【難以或無法控制的】 by endoscopic means such as dilation of benign【良性擴張】 or malignant strictures【惡性狹窄】,15-17 percutaneous endoscopic gastrostomy【經(jīng)皮內(nèi)鏡胃造口術(shù)】,18 and EUS-guided FNA【超聲內(nèi)鏡引導(dǎo)下細針穿刺活檢術(shù)】.19 Finally, patients requiring hemostasis【止血】 should be considered at higher risk of rebleeding regardless of whether their initial【最初的】 procedure was low risk.Condition risks【風(fēng)險條件】 The probability【概率】 of athromboembolic complication【并發(fā)癥】 related to the temporary【短暫的，臨時的】 interruption【中斷】 of antithrombotic therapy for an endoscopic procedure depends on the preexisting 【先前存在的】condition that resulted in the use of antithrombotic therapy.These conditions may be divided into low- and higher risk groups based on their associated risk of thromboembolic events (Table4).Low-risk conditions include DVT【深靜脈血栓形成】,chronic【慢性的】 or paroxysmal【陣發(fā)性】 atrial【心房的，中庭的】 fibrillation【纖維顫動】 not associated with valvular disease【瓣膜病】,bioprosthetic valves【生物瓣膜】,and mechanical valves【機械瓣膜】 in the aortic 【大動脈】position.Higher-risk conditions include atrial fibrillation associated with valvular heart disease【瓣膜性心臟病】 (whether surgically corrected or not),mechanical valves in the mitral position【二尖瓣位置】,and mechanical valves in patients who have had a previous【先前的、以前的】 thromboembolic event【血栓栓塞事件】. Patients with coronary【冠狀動脈】 stents 【支架】(especially those with a drug-eluting stent 【藥物釋放支架】DES) are at higher risk of stent thrombosis【血栓癥】, particularly when dual antiplatelet therapy【雙聯(lián)抗血小板治療】 (DAT)is discontinued【終止，中斷】 before minimum duration recommendations. Current【現(xiàn)在的，最近的】 guidelines【指南，指導(dǎo)方針】 from the American Heart Association (AHA)【美國心臟聯(lián)合會】 recommend that DAT should ideally【理論上地，完美地，理想地】 be continued for 12 months beyond the date of placement【放置，安置】 in patients with a DES.20TABLE 4. Condition risk for thromboembolic eventHigher-risk condition Low-risk conditionAtrial fibrillation associated Uncomplicated orwith valvular heart disease, paroxysmal nonvalvularprosthetic valves, active atrial fibrillationcongestive heart failure, Bioprosthetic valveleft ventricular ejection Mechanical valve in thefraction35%, a history aortic positionof a thromboembolic Deep vein thrombosisevent, hypertension,diabetes mellitus, orage 75 ymitral positionBioprosthetic valveMechanical valve in anyposition and previousthromboembolic eventRecently (1 y) placedcoronary stentAcute coronary syndromeNonstented percutaneouscoronary intervention aftermyocardial infarction The risk of major embolism【栓塞，栓子】 (causing death, residual neurologic deficit【殘余神經(jīng)功能缺損】, or peripheral ischemia requiring surgery【外周缺血需要外科手術(shù)】) in the absence【缺少，缺乏】 of antithrombotic therapy in patients with mechanical valves is 4 per 100 patient-years.21 With antiplatelet therapy, this risk is reduced to 2.2 per 100 patient-years and with warfarin to 1 per 100 patient-years.22 In a pooled analysis of 5 randomized controlled trials【在一個集中5個隨機對照試驗的分析】, nonanticoagulated patients with sustained【持續(xù)的】 atrial fibrillation【心房纖顫】 had an annual stroke rate of 4.5%.23 In patients with atrial fibrillation and concomitant dilated cardiomyopathy, valvular heart disease, or recent thromboembolic events, the risk of thromboembolism is greater.24 Anticoagulation therapy for DVT is typically performed for 1 to 6 months.25 Short-term discontinuation of anticoagulation therapy does not seem to significantly increase the risk of pulmonary embolism.ELECTIVE ENDOSCOPIC PROCEDURES IN PATIENTS RECEIVING ANTITHROMBOTIC THERAPY【選擇的內(nèi)窺鏡手術(shù)的病人接受抗凝治療】Risk of bleeding from specific procedures while taking antithrombotic agents Diagnostic endoscopy. Although aspirin has been shown to prolong【延長】 bleeding times as long as 48 hours after ingestion【攝取】,26,27 there are no clinical trials demonstrating【證明，證實】 an increased incidence【發(fā)生率】 of bleeding in patients who have undergone【經(jīng)歷，承受】 upper【較高的，上面的】 or lower endoscopy with and without biopsy【組織活檢】 while taking aspirin or clopidogre【氯吡格雷】l. Moreover, there is evidence【證據(jù)，跡象】 that continuing therapeutic【療法，治療學(xué)】 anticoagulation【抗凝】 with warfarin during the periendoscopic period【圍內(nèi)窺鏡期】 has a low risk of bleeding in such low-risk procedures. A retrospective 【回顧的】 study by Gerson et al28 of 104 patients who underwent【經(jīng)歷】 171 endoscopic procedures while maintaining【保持，堅持】 therapeutic【治療的，療法的】 warfarin dosing found that in low-risk procedures (upper【上面的】 endoscopy【內(nèi)鏡檢查術(shù)】 and colonoscopy【結(jié)腸鏡檢查】 including the use of mucosal biopsy), no clinically evident bleeding occurred【發(fā)生，出現(xiàn)】.28 Colonoscopic【結(jié)腸鏡檢查】 polypectomy【息肉切除術(shù)】. Several studies examined the risk of antithrombotic【抗血栓形成的】 therapy in postpolypectomy【息肉切除術(shù)后】 bleeding. Although 1 prospective【預(yù)期的，可能的】 study of 694 patients found a small (1%) increased risk of trace【追蹤，追溯】 postpolypectomy bleeding in patients taking aspirin or NSAIDs,29 other larger retrospective【回顧的】 studies did not find this association【聯(lián)想】.30,31 Because the absolute【絕對的，完全的】 risk of postpolypectomy bleeding seems to be low, even in the setting of aspirin or NSAID use, very large studies would be required to demonstrate【證明，證實】 a significantly【意義深長的，值得注目的】 elevated【升高的，高層的】 risk (if the risk was actually【確實，實際上】 increased). For example, to have an 80% power to detect a 50% increase in absolute risk of bleeding with aspirin or NSAIDs from 2% to 3%, more than 4000 patients would need to be included in each group. Thus far, there has not been a prospective study of this magnitude【巨大，重要】 conducted【引導(dǎo)，實施】. Although the data are limited, postpolypectomy bleeding risk seems to be increased for patients taking warfarin31,32 or resuming【重新開始】 warfarin or heparin within【在內(nèi)，不超過】 1 week after polypectomy.31 Case series of prophylactic【預(yù)防性的】 clip【夾子】 application after polypectomy of small polyps【息肉】 (1 cm) in patients taking antithrombotic agents demonstrate low rates of bleeding (0%-3.3%).32-35 However, no randomized【使隨機化】 controlled trials【隨機對照試驗】 in patients actively using antithrombotic agents have been performed【進行，完成，執(zhí)行】. Because of the lack of definitive【明確的，決定性的】 clinical data and associated costs【相關(guān)成本】, routine application【常規(guī)應(yīng)用】 of prophylactic mechanical【機械的】 clips or detachable【可拆開的，可分開的】 snares【可拆卸的的圈套】 in these patients cannot be recommended【推薦，建議】 at this time.Sphincterotomy【括約肌切開術(shù)】 and PEG. The overall【總的，全部的】 risk of postsphincterotomy bleeding is 0.3% to 2.0%.36-38 Withholding aspirin or NSAIDs, even as long as 7 days before sphincterotomy, does not seem to reduce the risk of bleeding.39 However, anticoagulation【抗凝作用】 with oral【口服的，口頭的】 warfarin or intravenous【靜脈注射】 heparin within 3 days after has been shown to increase the risk of postsphincterotomy bleeding.40 PEG placement has an overall bleeding complication【并發(fā)癥】 rate of approximately 2.5%.41,42 The risk of bleeding for PEG placement【安置，放置，定位】 in the patient receiving antithrombotic therapy is unknown.Risk of stopping antithrombotic therapy before elective endoscopy When antithrombotic therapy is temporary【臨時的，暫時的】, such as for DVT【深部靜脈血栓形成】, elective procedures should be delayed【推遲，延期】, if possible, until anticoagulation【抗凝】 is no longer indicated【標示，表明】. This is particularly true in patients with a recently placed coronary【冠狀動脈】 stent【支架】 (see detailed discussion below【請參閱下面的詳細討論】) who have significant risks of spontaneous【自發(fā)的，天然產(chǎn)生的】 stent occlusion【閉塞，堵塞】 with subsequent【隨后的，作為結(jié)果而發(fā)生的】 acute coronary syndrome【急性冠脈綜合征】 and death.43-45 If a decision is made to perform endoscopy in patients receiving antithrombotic therapy, the need to stop or reverse【交換，推翻】 these agents should be individualized【賦予個性，個別的加以考慮】. The administration【管理，施行】 of vitamin K to reverse anticoagulation for elective procedures should be avoided because it delays【延遲】 therapeutic anticoagulation【抗凝治療】 once anticoagulants【抗凝劑】 are resumed【重新開始，繼續(xù)】.46 The 2006 AHA/American College of Cardiology【心臟病學(xué)】 (ACC) guidelines recommend that in patients at low risk of thrombosis【血栓癥】 (Table 4) warfarin simply be held before the procedure and that bridge therapy with heparin is usually unnecessary. The absolute【絕對的，完全的】 risk of an embolic【栓子的】 event【事件】 for patients in whom anticoagulation is interrupted for 4 to 7 days is approximately【近似的，大約】 1%.47,48 In 1 large prospective【預(yù)期的，未來的，可能的】 multicenter【多中心，多通道】 observational study, almost 1300 cases【事例】 (in 1024 patients) of warfarin interruption【中斷，打斷】 were examined.47 The most common indications【最常見的適應(yīng)癥】 for anticoagulation were atrial fibrillation (43%), venous thrombosis【靜脈血栓形成】 (11%), and mechanical heart valves【瓣膜】 (10%). Only 73 patients were considered at higher risk of thromboembolism【血栓栓塞】, with 93% of the patients deemed【認為，視為】 at low risk. Only 7 (0.7%) patients had a postprocedure 【術(shù)后】 thromboembolic event within 30 days of the procedure, although more than 80% of the total study population had anticoagulation held for less than 5 days. None of the 7 patients who experienced a thromboembolic event received bridging therapy (ie, short-acting anticoagulation medication use), despite【盡管】 the fact that 2 of these patients were technically high risk 【技術(shù)風(fēng)險高】because of active malignancy【主動惡化】 and recent DVT,