國家衛(wèi)生計(jì)生委公益性行業(yè)科研專項(xiàng)《關(guān)節(jié)置換術(shù)安全性與效果評(píng)價(jià)》項(xiàng)目組

岳辰1周宗科1裴福興1**翁習(xí)生2**邱貴興2**阮長耿3**

（1.四川大學(xué)華西醫(yī)院骨科，成都610041；2.中國醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)院骨科，北京100730；3.江蘇省血液研究所，蘇州215006）

·專家共識(shí)·

中國髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期抗纖溶藥序貫抗凝血藥應(yīng)用方案的專家共識(shí)*

國家衛(wèi)生計(jì)生委公益性行業(yè)科研專項(xiàng)《關(guān)節(jié)置換術(shù)安全性與效果評(píng)價(jià)》項(xiàng)目組

岳辰1周宗科1裴福興1**翁習(xí)生2**邱貴興2**阮長耿3**

（1.四川大學(xué)華西醫(yī)院骨科，成都610041；2.中國醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)院骨科，北京100730；3.江蘇省血液研究所，蘇州215006）

髖、膝關(guān)節(jié)置換術(shù)?？砂殡S大量失血。根據(jù)文獻(xiàn)報(bào)道，髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期總失血量多在1000m l以上，輸血率高達(dá)30%～60%[1,2]。大量失血可增加患者的圍術(shù)期風(fēng)險(xiǎn)和經(jīng)濟(jì)負(fù)擔(dān)[3]。髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期失血除手術(shù)切口直接出血外，由手術(shù)創(chuàng)傷引起的纖溶反應(yīng)增強(qiáng)所致的失血約占總失血量的60%[4]。而且，膝關(guān)節(jié)置換術(shù)中應(yīng)用止血帶引起的組織缺血再灌注損傷可進(jìn)一步增強(qiáng)纖溶反應(yīng)[5]，增加出血量。

氨甲環(huán)酸（tranexam ic acid，TXA）是一種抗纖溶藥，其與纖溶酶原的賴氨酸結(jié)合位點(diǎn)具有高親和性，可封閉纖溶酶原的賴氨酸結(jié)合位點(diǎn)，使纖溶酶原失去與纖維蛋白結(jié)合的能力，導(dǎo)致纖溶活性降低，從而發(fā)揮止血作用[6]。目前，大量研究均已證實(shí)氨甲環(huán)酸能有效減少髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期的失血量并降低輸血率，且不增加術(shù)后靜脈血栓栓塞癥的發(fā)生風(fēng)險(xiǎn)[5-8]。

髖、膝關(guān)節(jié)置換術(shù)患者是靜脈血栓栓塞癥的高發(fā)人群，應(yīng)用抗凝血藥物能有效降低靜脈血栓栓塞癥的發(fā)生率。為了在髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期更好地平衡抗纖溶藥與抗凝血藥的應(yīng)用，既可減少患者的出血量、降低輸血率，又不增加患者發(fā)生靜脈血栓栓塞癥的風(fēng)險(xiǎn)，保障醫(yī)療安全。國家衛(wèi)生計(jì)生委公益性行業(yè)科研專項(xiàng)《關(guān)節(jié)置換術(shù)安全性與效果評(píng)價(jià)》項(xiàng)目組（項(xiàng)目編號(hào)：201302007）和《中華骨與關(guān)節(jié)外科雜志》編輯部邀請(qǐng)國內(nèi)專家，復(fù)習(xí)國內(nèi)外27篇meta分析和260多篇論著，結(jié)合項(xiàng)目組26家大型醫(yī)院數(shù)據(jù)庫和50家推廣醫(yī)院數(shù)據(jù)庫共13300例髖、膝關(guān)節(jié)置換術(shù)病例中8426例氨甲環(huán)酸應(yīng)用經(jīng)驗(yàn)以及全國12場氨甲環(huán)酸臨床應(yīng)用區(qū)域會(huì)議征求意見結(jié)果，遵循循證醫(yī)學(xué)原則，達(dá)成髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期抗纖溶藥序貫抗凝血藥應(yīng)用的專家共識(shí)，供廣大骨科醫(yī)師在臨床工作中參考應(yīng)用。但在應(yīng)用氨甲環(huán)酸前應(yīng)結(jié)合患者的全身情況，參照氨甲環(huán)酸藥物說明書或《中國藥典》，遇有不良反應(yīng)及時(shí)處理。

1 髖關(guān)節(jié)置換術(shù)圍術(shù)期的氨甲環(huán)酸應(yīng)用

1.1 靜脈應(yīng)用

11篇meta分析[8-18]及19篇前瞻性隨機(jī)對(duì)照研究[19-37]報(bào)道氨甲環(huán)酸給藥方式主要為單次靜脈滴注或二次間隔靜脈滴注，二次給藥間隔時(shí)間為3 h。單次給藥劑量為15～20mg/kg或總量1 g；二次間隔給藥劑量為每次10～20mg/kg或每次總量1 g。

推薦：①單次給藥法：髖關(guān)節(jié)置換術(shù)切開皮膚前5～10m in氨甲環(huán)酸15～20mg/kg或總量1 g靜脈滴注完畢；②二次間隔給藥法：首次給藥同單次給藥法，3 h后根據(jù)引流情況再次給藥，劑量同前。

1.2 局部應(yīng)用

研究表明，氨甲環(huán)酸局部應(yīng)用能夠提高局部藥物濃度，減少全身吸收[38]。1篇meta分析[39]及4篇前瞻性隨機(jī)對(duì)照研究[38,40-42]報(bào)道氨甲環(huán)酸2～3 g局部應(yīng)用可以有效減少出血、降低輸血率。目前，有關(guān)氨甲環(huán)酸的局部應(yīng)用尚無統(tǒng)一標(biāo)準(zhǔn)，特別是對(duì)于術(shù)后是否放置引流管及引流管夾閉后何時(shí)開放仍存在爭議，各報(bào)道中術(shù)后引流管夾閉時(shí)間為30m in～2 h不等。因此，氨甲環(huán)酸在髖關(guān)節(jié)置換術(shù)中局部應(yīng)用的具體方法及術(shù)后引流管夾閉時(shí)間有待進(jìn)一步研究。

推薦：氨甲環(huán)酸在髖關(guān)節(jié)置換術(shù)中局部應(yīng)用的推薦劑量為2～3 g。

1.3 靜脈和局部聯(lián)合應(yīng)用

研究報(bào)道，氨甲環(huán)酸在髖關(guān)節(jié)置換術(shù)圍術(shù)期靜脈滴注聯(lián)合局部應(yīng)用相比單純靜脈滴注或局部應(yīng)用能更有效減少出血、降低輸血率[43]。具體方法為髖關(guān)

節(jié)置換術(shù)切開皮膚前5～10m in氨甲環(huán)酸15～20mg/kg靜脈滴注完畢，同時(shí)關(guān)閉切口前以總量1～2 g氨甲環(huán)酸局部應(yīng)用。

推薦：髖關(guān)節(jié)置換術(shù)切開皮膚前5～10m in氨甲環(huán)酸15～20mg/kg靜脈滴注完畢，同時(shí)關(guān)閉切口前氨甲環(huán)酸1～2 g局部應(yīng)用。

2 膝關(guān)節(jié)置換術(shù)圍術(shù)期的氨甲環(huán)酸應(yīng)用

2.1 靜脈應(yīng)用

13篇meta分析[7,9,44-54]及16篇前瞻隨機(jī)對(duì)照研究[5,19,55-68]報(bào)道，氨甲環(huán)酸給藥方式主要為單次靜脈滴注或二次間隔靜脈滴注，二次給藥間隔為3 h。單次給藥時(shí)間應(yīng)在手術(shù)開始前（不用止血帶者）或松止血帶前5～10m in，劑量為10～20mg/kg或總量1 g；二次給藥時(shí)間為首次給藥后3 h再次給藥，劑量為每次10～20mg/kg或每次總量1 g。

推薦：①單次給藥法：膝關(guān)節(jié)置換術(shù)切開皮膚前（不用止血帶者）或松止血帶前5～10 m in氨甲環(huán)酸10～20 mg/kg或1 g靜脈滴注完畢；②二次間隔給藥法：首次給藥同單次給藥法，3 h后根據(jù)引流情況再次給藥，劑量相同。

2.2 局部應(yīng)用

4篇meta分析[69-72]及12篇前瞻隨機(jī)對(duì)照研究[73-79]報(bào)道氨甲環(huán)酸局部應(yīng)用的最低有效劑量≥2 g[70]、最低有效濃度≥20 mg/m l[71]，大劑量（≥2 g）和高濃度（≥20mg/m l）氨甲環(huán)酸局部應(yīng)用能有效減少膝關(guān)節(jié)置換術(shù)圍術(shù)期出血、降低輸血率。局部應(yīng)用方法為關(guān)閉切口前關(guān)節(jié)腔灌注，或關(guān)閉切口后通過引流管逆行注入，或通過注射器關(guān)節(jié)腔內(nèi)注射。各報(bào)道中術(shù)后引流管夾閉時(shí)間為30m in～2 h不等，仍存在爭議，有待進(jìn)一步研究。

推薦：氨甲環(huán)酸在膝關(guān)節(jié)置換術(shù)中的局部應(yīng)用應(yīng)在關(guān)閉切口前后，局部應(yīng)用的劑量≥2 g或濃度≥20mg/m l。

2.3 靜脈和局部聯(lián)合應(yīng)用

聯(lián)合給藥方法為松開止血帶5～10m in前氨甲環(huán)酸15～20 mg/kg或1 g靜脈滴注，同時(shí)關(guān)閉切口前氨甲環(huán)酸1～2 g局部注入。聯(lián)合用藥能有效減少膝關(guān)節(jié)置換術(shù)圍術(shù)期出血、降低輸血率[80]。

推薦：膝關(guān)節(jié)置換術(shù)切開皮膚前（不用止血帶者）或松止血帶前5～10m in氨甲環(huán)酸15～20mg/kg或1 g靜脈滴注完畢，同時(shí)關(guān)閉切口前氨甲環(huán)酸1～2 g局部應(yīng)用。

3 髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期抗纖溶藥序貫抗凝血藥應(yīng)用

髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期應(yīng)用抗纖溶藥氨甲環(huán)酸后序貫應(yīng)用抗凝血藥，既能減少出血，又不增加靜脈血栓栓塞癥發(fā)生風(fēng)險(xiǎn)。氨甲環(huán)酸的止血效果與其應(yīng)用劑量和應(yīng)用次數(shù)有關(guān)，但隨著劑量或次數(shù)的增加，靜脈血栓栓塞癥的發(fā)生風(fēng)險(xiǎn)也可能增大。理論上認(rèn)為，抗凝血藥物在術(shù)后應(yīng)用越早、持續(xù)時(shí)間越長，患者發(fā)生靜脈血栓栓塞癥的風(fēng)險(xiǎn)越小，但發(fā)生出血的風(fēng)險(xiǎn)增大。為了達(dá)到抗纖溶藥和抗凝血藥的平衡，應(yīng)在髖、膝關(guān)節(jié)置換術(shù)圍術(shù)期應(yīng)用氨甲環(huán)酸6 h后根據(jù)引流量的變化，選擇抗凝血藥應(yīng)用時(shí)間。大部分患者術(shù)后6～12 h內(nèi)傷口出血趨于停止，如引流管無明顯出血或引流管血清已分離則表明傷口出血趨于停止，應(yīng)在12 h內(nèi)應(yīng)用抗凝血藥；若個(gè)別患者術(shù)后12 h仍有明顯出血，可延后應(yīng)用抗凝血藥。

髖、膝關(guān)節(jié)置換術(shù)后抗凝血藥物預(yù)防持續(xù)時(shí)間應(yīng)根據(jù)《中國骨科大手術(shù)靜脈血栓栓塞癥預(yù)防指南》，推薦預(yù)防時(shí)間最短為10 d，可延長至11～35 d[81]。在應(yīng)用時(shí)應(yīng)注意抗凝血藥物的有效性和安全性，當(dāng)患者出現(xiàn)凝血功能異?；虺鲅录r(shí)，應(yīng)綜合評(píng)價(jià)出血與血栓的風(fēng)險(xiǎn)，及時(shí)調(diào)整藥物劑量或停用。

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2095-9958（2015）08-0 281-05

10.3969/j.issn.2095-9958.2015.04-001

國家衛(wèi)生計(jì)生委公益性行業(yè)科研專項(xiàng)（項(xiàng)目編號(hào)：201302007）

**通信作者：裴福興，E-mail：peifuxing@vip.163.com；翁習(xí)生，E-mail：xshw eng@medmail.com.cn；邱貴興，E-mail：qguixing@126.com；阮長耿，E-mail：changgengruan@hotmail.com