第一篇：肺栓塞-从病理机转到诊断治疗策略 台湾内科学志 2014_图概要
312 的病患，若 MDCT 結果正常，就足以排除肺栓 塞。至於臨床評估可能是肺栓塞，但 MDCT 結 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 或肺動脈 攝影(pulmonary angiography，則仍有爭議。不 過如果在臨床評估為肺栓塞中高度可能性，且 MDCT 發現在肺段動脈或更近端動脈分支有血 栓，則可確診肺栓塞。(二 肺栓塞高危險群的診斷原則 研究顯示，MDCT 應用於血液動力學不穩 定的肺栓塞高危險群病患上，其偵測肺主動脈(main pulmonary artery 栓塞的敏感度(sensitivity 約達 97%，因此建議這群高危險病患在狀況允 許之下，應接受 MDCT 檢查 35,40 一、抗凝血治療(Anticoagulation therapy 肺栓塞的初期治療目標是盡快使肺血管床 恢復足夠血流，並且避免再復發。針對臨床 評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。初期治療的標準 抗 凝 血 劑 包 括 傳 統 肝 素(unfractionated heparin, UFH、靜 脈 注 射 型 傳 統 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。對於肺栓塞中低危險群病患，傾向選擇 LMWH 治療，相對地，已出現週邊灌流損傷而 導致皮下吸收能力變差之嚴重栓
塞者，則宜接 受注射型傳統肝素治療 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 準 化 比 值(international normalized ratio, INR 達 2.0 且持續至少 1 天 3。Rivaroxaban 和 Dabigatran 是 新 一 代 口 服 抗 凝 血 劑。Rivaroxaban 的 作 用 機 轉 是 直 接 抑 制 凝 血 因 子 Xa，Dabigatran 則 是 一 種 前 驅 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、以口服方式給藥，且和 warfarin 相 比，藥物交互作用較少，也不需常規監測凝血 參數。研究顯示，這些新型口服抗凝血劑在預 防和治療靜脈栓塞上也有不錯的效果 43。所有肺栓塞病患都應接受長期抗凝血治 療，以避免栓子在全身蔓延，同時也降低復發 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。對於知道誘發因素(provoked 的肺栓塞患 者，建 議 治 療 3 個 月； 不 明 原 因(unprovoked 且無易出血危險因子之肺栓塞患者，建議治療 3-12 個月；若為復發性肺栓塞，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使用抗凝血劑治療 相比，擁有更快溶解血栓以改善肺部組織灌流 的優點，因此常用於血液動力學不穩定這類急。這類高危險 群病患若在肺循環中確實有血栓情形，則多為 較嚴重的栓塞，通常都能從 MDCT 檢查中得到 確診。由於這些病患的血液動力學處於不穩定狀 態，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症 如主動脈剝離、急性嚴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 有發現右心室負荷過重(overload 或功能受損，則可排除肺栓塞，另尋造成血液動力學不穩定 的病因。相對地，當心臟超音波顯示右心室負 荷過重或功能受損時，雖然大部分血液動力學 不穩定的肺栓塞病患，都能於經食道心臟超音 波檢查中看到肺主動脈血栓，還是建議待病患 狀況穩定後，再接受 MDCT 以確診。如果病患 狀況仍不適合做 MDCT 檢查，或者醫療院所沒 有其他檢測工具供進一步診斷，則以該心臟超 音波結果做為肺栓塞診斷。35 治療計畫 肺栓塞病患的血液動力學穩定與否和短 期預後有強烈相關性，一般而言，非高危險 群的預後較好 36, 41。因此內科治療計畫
主要是 依據血液動力學穩定度，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群病患 46。為避免 發生不可逆的心因性休克，對於血液動力學不 穩定的病患，不應延遲施行全身性血栓溶解治 療。至於出現急性右心室功能受損及心肌損 傷，但沒有明顯血液動力學阻礙的病患，可 能是早期預後不佳的中度危險群，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 會測到升高的數值而降低特異性，因此近年陸 續有以年齡校正 D-二聚體臨界值(age adjusted D-dimer cut-off point 配合臨床檢測前機率來排 除肺栓塞可能性的研究發表 52-54，希望藉此可排 除較多肺栓塞低風險的老年病患。雖然急性肺 栓塞是可致命的心血管急症，但若能及早診斷 處理，不僅可使缺損的右心室功能回復，也能 降低死亡風險。雖然全身性血栓溶 解治療可以改善血液動力學的不穩定性以及促 進右心室功能恢復，不過可能出現高達 20% 的 大 出 血 和 3% 的 顱 內 出 血 等 併 發 症 36,50。最近一項利用超音波輔助加速肺栓塞血栓溶解治療 的 多 中 心 隨 機 對 照 試 驗(Ultrasound accelerated thrombolysis of pulmonary embolism, ULTIMA，針 對 肺 栓 塞 中 度 危 險 群 病 患，以 固 定 劑 量(fixed-dose、超 音 波 輔 助(ultrasound-assisted、導 管 介 入(catheter-directed 方 式，給 予 血 栓 溶 解 劑(recombinant tissue plasminogen activator, rt-PA，發現在治療 24 小時的右心室功能改善效 果勝於單獨給予肝素抗凝血劑(heparin，而且 不會增加出血併發症的機率 51。不過這項研究缺 少無超音波輔助之血栓溶解治療對照組，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。對於這些血液動力學不穩定的嚴重肺栓塞 病患，美國心臟學會在 2011 年的肺栓塞治療準 則中建議 46，若對血栓溶解劑有使用禁忌症或 是血栓溶解劑治療失敗，可選擇以外科栓塞切 除 術(surgical embolectomy 或 導 管 式 血 栓 清 除(catheter embolectomy 作為替代或進階處置。參考文獻 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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