第一篇：肺栓塞-從病理機(jī)轉(zhuǎn)到診斷治療策略 臺(tái)灣內(nèi)科學(xué)志 2014_圖概要

312 的病患，若 MDCT 結(jié)果正常，就足以排除肺栓 塞。至於臨床評(píng)估可能是肺栓塞，但 MDCT 結(jié) 果正常，是否須另做其他檢查包括下肢靜脈壓 迫 超 音 波(compression venous ultrasonography, CUS 或 / 和換氣攝影(V/Q scintigraphy 或肺動(dòng)脈 攝影(pulmonary angiography，則仍有爭議。不 過如果在臨床評(píng)估為肺栓塞中高度可能性，且 MDCT 發(fā)現(xiàn)在肺段動(dòng)脈或更近端動(dòng)脈分支有血 栓，則可確診肺栓塞。(二 肺栓塞高危險(xiǎn)群的診斷原則 研究顯示，MDCT 應(yīng)用於血液動(dòng)力學(xué)不穩(wěn) 定的肺栓塞高危險(xiǎn)群病患上，其偵測肺主動(dòng)脈(main pulmonary artery 栓塞的敏感度(sensitivity 約達(dá) 97%，因此建議這群高危險(xiǎn)病患在狀況允 許之下，應(yīng)接受 MDCT 檢查 35,40 一、抗凝血治療(Anticoagulation therapy 肺栓塞的初期治療目標(biāo)是盡快使肺血管床 恢復(fù)足夠血流，並且避免再復(fù)發(fā)。針對(duì)臨床 評(píng)估可能是肺栓塞的病患，一般建議在診斷階 段過程中就開始抗凝血治療。初期治療的標(biāo)準(zhǔn) 抗 凝 血 劑 包 括 傳 統(tǒng) 肝 素(unfractionated heparin, UFH、靜 脈 注 射 型 傳 統(tǒng) 肝 素、第 Xa 因 子 抑 制 劑 Fondaparinux 以 及 皮 下 給 藥 之 低 分 子 量 heparin(low-molecular-weight heparin, LMWH 等 42。對(duì)於肺栓塞中低危險(xiǎn)群病患，傾向選擇 LMWH 治療，相對(duì)地，已出現(xiàn)週邊灌流損傷而 導(dǎo)致皮下吸收能力變差之嚴(yán)重栓

塞者，則宜接 受注射型傳統(tǒng)肝素治療 41，最短 5 天後才能停 藥。此外，這些療程尚須搭配維生素 K 拮抗劑(vitamin-K antagonists, VKAs 治療，確保國際標(biāo) 準(zhǔn) 化 比 值(international normalized ratio, INR 達(dá) 2.0 且持續(xù)至少 1 天 3。Rivaroxaban 和 Dabigatran 是 新 一 代 口 服 抗 凝 血 劑。Rivaroxaban 的 作 用 機(jī) 轉(zhuǎn) 是 直 接 抑 制 凝 血 因 子 Xa，Dabigatran 則 是 一 種 前 驅(qū) 藥(prodrug，其活性代謝物為競爭性的直接凝血 抑 制 劑(direct thrombin inhibitor, DTI。這 些 藥物的共通特性包括：低分子量、半衰期短(約 8-16 小時(shí)、以口服方式給藥，且和 warfarin 相 比，藥物交互作用較少，也不需常規(guī)監(jiān)測凝血 參數(shù)。研究顯示，這些新型口服抗凝血?jiǎng)┰陬A(yù) 防和治療靜脈栓塞上也有不錯(cuò)的效果 43。所有肺栓塞病患都應(yīng)接受長期抗凝血治 療，以避免栓子在全身蔓延，同時(shí)也降低復(fù)發(fā) 可能性。長期抗凝血治療中最常使用的藥物為 VKAs，通常於肺栓塞確診後即可馬上開始給 藥。對(duì)於知道誘發(fā)因素(provoked 的肺栓塞患 者，建 議 治 療 3 個(gè) 月； 不 明 原 因(unprovoked 且無易出血危險(xiǎn)因子之肺栓塞患者，建議治療 3-12 個(gè)月；若為復(fù)發(fā)性肺栓塞，則宜接受無限 期治療 44-45。二、血栓溶解治療(Thrombolytic therapy 血栓溶解治療和單獨(dú)使用抗凝血?jiǎng)┲委?相比，擁有更快溶解血栓以改善肺部組織灌流 的優(yōu)點(diǎn)，因此常用於血液動(dòng)力學(xué)不穩(wěn)定這類急。這類高危險(xiǎn) 群病患若在肺循環(huán)中確實(shí)有血栓情形，則多為 較嚴(yán)重的栓塞，通常都能從 MDCT 檢查中得到 確診。由於這些病患的血液動(dòng)力學(xué)處於不穩(wěn)定狀 態(tài)，如果因故無法立即做 MDCT 檢查，則必須 安排床邊心臟超音波，盡快和其他心血管急癥 如主動(dòng)脈剝離、急性嚴(yán)重瓣膜疾病或心包膜填 塞(tamponade 等做鑑別診斷。若心臟超音波沒 有發(fā)現(xiàn)右心室負(fù)荷過重(overload 或功能受損，則可排除肺栓塞，另尋造成血液動(dòng)力學(xué)不穩(wěn)定 的病因。相對(duì)地，當(dāng)心臟超音波顯示右心室負(fù) 荷過重或功能受損時(shí)，雖然大部分血液動(dòng)力學(xué) 不穩(wěn)定的肺栓塞病患，都能於經(jīng)食道心臟超音 波檢查中看到肺主動(dòng)脈血栓，還是建議待病患 狀況穩(wěn)定後，再接受 MDCT 以確診。如果病患 狀況仍不適合做 MDCT 檢查，或者醫(yī)療院所沒 有其他檢測工具供進(jìn)一步診斷，則以該心臟超 音波結(jié)果做為肺栓塞診斷。35 治療計(jì)畫 肺栓塞病患的血液動(dòng)力學(xué)穩(wěn)定與否和短 期預(yù)後有強(qiáng)烈相關(guān)性，一般而言，非高危險(xiǎn) 群的預(yù)後較好 36, 41。因此內(nèi)科治療計(jì)畫

主要是 依據(jù)血液動(dòng)力學(xué)穩(wěn)定度，大致上分成抗凝血 治 療(anticoagulation therapy 和 血 栓 溶 解 治 療(thrombolytic therapy 等方式。

313 需移除栓子的肺栓塞高危險(xiǎn)群病患 46。為避免 發(fā)生不可逆的心因性休克，對(duì)於血液動(dòng)力學(xué)不 穩(wěn)定的病患，不應(yīng)延遲施行全身性血栓溶解治 療。至於出現(xiàn)急性右心室功能受損及心肌損 傷，但沒有明顯血液動(dòng)力學(xué)阻礙的病患，可 能是早期預(yù)後不佳的中度危險(xiǎn)群，也建議須及 早接受再灌流治療 36,48,49 47 由於 D-二聚體檢測在一些特定族群如老年人也 會(huì)測到升高的數(shù)值而降低特異性，因此近年陸 續(xù)有以年齡校正 D-二聚體臨界值(age adjusted D-dimer cut-off point 配合臨床檢測前機(jī)率來排 除肺栓塞可能性的研究發(fā)表 52-54，希望藉此可排 除較多肺栓塞低風(fēng)險(xiǎn)的老年病患。雖然急性肺 栓塞是可致命的心血管急癥，但若能及早診斷 處理，不僅可使缺損的右心室功能回復(fù)，也能 降低死亡風(fēng)險(xiǎn)。雖然全身性血栓溶 解治療可以改善血液動(dòng)力學(xué)的不穩(wěn)定性以及促 進(jìn)右心室功能恢復(fù)，不過可能出現(xiàn)高達(dá) 20% 的 大 出 血 和 3% 的 顱 內(nèi) 出 血 等 併 發(fā) 癥 36,50。最近一項(xiàng)利用超音波輔助加速肺栓塞血栓溶解治療 的 多 中 心 隨 機(jī) 對(duì) 照 試 驗(yàn)(Ultrasound accelerated thrombolysis of pulmonary embolism, ULTIMA，針 對(duì) 肺 栓 塞 中 度 危 險(xiǎn) 群 病 患，以 固 定 劑 量(fixed-dose、超 音 波 輔 助(ultrasound-assisted、導(dǎo) 管 介 入(catheter-directed 方 式，給 予 血 栓 溶 解 劑(recombinant tissue plasminogen activator, rt-PA，發(fā)現(xiàn)在治療 24 小時(shí)的右心室功能改善效 果勝於單獨(dú)給予肝素抗凝血?jiǎng)?heparin，而且 不會(huì)增加出血併發(fā)癥的機(jī)率 51。不過這項(xiàng)研究缺 少無超音波輔助之血栓溶解治療對(duì)照組，因此 超音波在血栓溶解治療中扮演的角色仍有待更 多研究來釐清。對(duì)於這些血液動(dòng)力學(xué)不穩(wěn)定的嚴(yán)重肺栓塞 病患，美國心臟學(xué)會(huì)在 2011 年的肺栓塞治療準(zhǔn) 則中建議 46，若對(duì)血栓溶解劑有使用禁忌癥或 是血栓溶解劑治療失敗，可選擇以外科栓塞切 除 術(shù)(surgical embolectomy 或 導(dǎo) 管 式 血 栓 清 除(catheter embolectomy 作為替代或進(jìn)階處置。參考文獻(xiàn) 1.Kucher N.Deep-vein thrombosis of the upper extremities.N Engl J Med 2011;364: 861-9.2.Goldhaber SZ, Bounameaux H.Pulmonary embolism and deep vein thrombosis.Lancet 2012;379: 1835-46.3.L apner ST, Kearon C.Diagnosis and management of pulmonary embolism.BMJ 2013;346: f757.4.Heit JA.The epidemiology of venous

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thromboembolism history and physical examination instead of considering pulmonary embolism and deep venous thrombosis as independent diseases.The symptoms and signs of pulmonary embolism range widely and are often non-specific.The current diagnostic strategy of pulmonary embolism is to evaluate hemodynamic status first.In patients with hemodynamic stability, the diagnosis should follow a sequential diagnostic workup consisting of clinical pre-test probability, d-dimer testing, and diagnostic imaging by such techniques as multidetector computed tomography.Pulmonary embolism is one of the most common causes of vascular death after myocardial infarction and stroke;it is also the leading preventable cause of death in hospitalized patients in the United States.Therefore, the rapid diagnosis, effective management, and preventive assessment of pulmonary embolism may lower the risk of lethal complications, despite its high mortality rate.(J Intern Med Taiwan 2014;25: 307-315