王百盛，　劉欣偉，　張敬東，　韓文鋒，　何　勇，　劉海立

沈陽(yáng)軍區(qū)總醫(yī)院 骨科，遼寧 沈陽(yáng)　110016

·論著·

重組人促紅素與蔗糖鐵在人工全髖關(guān)節(jié)置換術(shù)圍術(shù)期中應(yīng)用

王百盛，劉欣偉，張敬東，韓文鋒，何勇，劉海立

沈陽(yáng)軍區(qū)總醫(yī)院 骨科，遼寧 沈陽(yáng)110016

摘要：目的觀察重組人促紅素(rhEPO)與蔗糖鐵在人工全髖關(guān)節(jié)置換術(shù)(THA)圍術(shù)期中的應(yīng)用療效。方法選取自2015年9月至2016年3月沈陽(yáng)軍區(qū)總醫(yī)院骨科收治的THA患者97例，按隨機(jī)數(shù)字表分法分為對(duì)照組(48例)與觀察組(49例)。對(duì)照組患者視血紅蛋白(Hb)情況，給予口服鐵劑，并在飲食中補(bǔ)充。觀察組患者于手術(shù)前3 d開始，給予rhEPO，150 IU/kg皮下注射，每天1次，至術(shù)后第7天；同時(shí)，給予蔗糖鐵100 mg靜脈輸液，每周3次。分別于手術(shù)后1、3、5、7 d 觀察兩組患者Hb含量和紅細(xì)胞計(jì)數(shù)(RBC)的變化情況。結(jié)果術(shù)后，觀察組患者Hb含量明顯高于對(duì)照組，兩組間比較，差異有統(tǒng)計(jì)學(xué)意義(P<0.05)；觀察組患者的RBC水平也明顯高于對(duì)照組，兩組間比較，差異也有統(tǒng)計(jì)學(xué)意義(P<0.05)。結(jié)論聯(lián)合應(yīng)用rhEPO與蔗糖鐵治療THA圍術(shù)期貧血，效果滿意，既能避免異體輸血的相關(guān)風(fēng)險(xiǎn)，又能緩解目前用血緊張狀態(tài)。

關(guān)鍵詞：重組人促紅素；蔗糖鐵注射液；髖關(guān)節(jié)置換；圍術(shù)期；貧血

DOI∶10.16048/j.issn.2095-5561.2016.03.05

人工全髖關(guān)節(jié)置換術(shù)(total hip arthroplasty，THA)是治療高齡股骨頸骨折、股骨頭無(wú)菌性壞死等疾病的有效且成功的手術(shù)方式[1]。該手術(shù)創(chuàng)傷大，軟組織剝離多，是目前公認(rèn)的失血量最多的手術(shù)之一[2]。術(shù)后貧血常導(dǎo)致患者下床時(shí)間推遲，關(guān)節(jié)功能恢復(fù)緩慢，嚴(yán)重影響手術(shù)療效[3]。目前，異體輸血是糾正THA術(shù)后貧血最快、最有效的治療方式；但在臨床工作中，經(jīng)常面臨血源緊張及輸血的各種風(fēng)險(xiǎn)[4-5]。重組人促紅素(recombinant human erythropoietin，rhEPO)是一種通過基因重組技術(shù)在體外產(chǎn)生的活性糖蛋白，能夠與紅細(xì)胞表面的紅細(xì)胞生成素受體結(jié)合，刺激骨髓中紅系造血母細(xì)胞的增殖和分化，從而改善貧血癥狀[6]。本研究應(yīng)用rhEPO聯(lián)合蔗糖鐵治療THA圍術(shù)期貧血，臨床療效滿意。現(xiàn)報(bào)道如下。

1資料與方法

1.1一般資料選取自2015年9月至2016年3月沈陽(yáng)軍區(qū)總醫(yī)院骨科收治的THA患者97例，按隨機(jī)數(shù)字表法分為對(duì)照組(48例)及觀察組(49例)。對(duì)照組：男性19例，女性29例；平均年齡(62.0±6.9)歲。觀察組：男性19例，女性30例；平均年齡(66.0±8.5)歲。所有患者中，新鮮股骨頸骨折48例，陳舊性股骨頸骨折8例，股骨頭無(wú)菌性壞死31例，先天性髖關(guān)節(jié)發(fā)育不良及髖關(guān)節(jié)骨性關(guān)節(jié)炎10例。所有THA假體均為強(qiáng)生公司pinnacle生物全髖關(guān)節(jié)(全陶)假體，且均為初次行單側(cè)THA患者；排除雙側(cè)THA、人工半髖關(guān)節(jié)置換和髖關(guān)節(jié)翻修患者。兩組患者在性別、年齡、體質(zhì)量、血紅蛋白(hemoglobin，Hb)水平、紅細(xì)胞計(jì)數(shù)(red blood count，RBC)等一般資料比較，差異均無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)，具有可比性(表1)。

組別性別/例(百分率/%)男性女性年齡/歲體質(zhì)量/kgHb/g·L-1RBC/×1012個(gè)·L-1對(duì)照組(n=48)19(39.6)29(60.4)62.0±6.962.0±6.8129.2±11.14.2±1.4觀察組(n=49)19(38.8)30(61.2)66.0±8.564.0±8.1131.8±10.44.2±1.1P值>0.05>0.05>0.05>0.05>0.05

1.2治療方法對(duì)照組：采用口服鐵劑治療及有效的飲食指導(dǎo)，當(dāng)患者Hb<70 g/L時(shí)，適量給予輸血。觀察組：嚴(yán)格按照醫(yī)囑執(zhí)行，于手術(shù)前3 d開始，給予rhEPO，150 IU/kg皮下注射，每天1次，至術(shù)后第7天；同時(shí)，靜脈補(bǔ)充蔗糖鐵100 mg，每周3次。

1.3觀察指標(biāo)分別于用藥前及術(shù)后1、3、5、7 d觀察兩組患者Hb和RBC的變化情況，以及患者不良反應(yīng)情況。

2結(jié)果

2.1兩組患者用藥前、后Hb水平比較用藥前，兩組患者Hb水平比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；術(shù)后，觀察組患者各時(shí)間點(diǎn)Hb水平均明顯高于對(duì)照組，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。見表2。

組別用藥前術(shù)后1d3d5d7d對(duì)照組129.2±11.1107.2±11.792.3±14.694.0±11.296.2±12.0觀察組131.8±10.4112.4±12.798.1±11.2101.7±13.8105.4±11.3P值>0.05<0.05<0.05<0.05<0.05

2.2兩組患者用藥前、后RBC比較用藥前，兩組患者RBC比較，差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)；術(shù)后，觀察組患者各時(shí)間點(diǎn)RBC均明顯高于對(duì)照組，差異均有統(tǒng)計(jì)學(xué)意義(P<0.05)。見表3。

組別用藥前術(shù)后1d3d5d7d對(duì)照組4.2±1.43.4±1.42.8±1.53.0±1.43.1±1.6觀察組4.2±1.23.6±1.43.1±1.63.3±1.63.5±1.5P值>0.05<0.05<0.05<0.05<0.05

2.3不良反應(yīng)用藥過程中，兩組患者均未發(fā)生明顯的不良反應(yīng)。

3討論

目前，THA是治療嚴(yán)重髖關(guān)節(jié)疾病可靠的手術(shù)方法，手術(shù)量逐年增加[7]。一般情況下，THA假體15～20年生存率為70%～80%，而且置換后能夠立即達(dá)到緩解疼痛、矯正畸形的目的，極大提高患者的生存質(zhì)量[8-9]。THA作為一項(xiàng)擇期手術(shù)，存在大量失血和異體輸血率較高等血液管理問題[10]。Rosencher等[11]的歐洲多中心調(diào)查顯示，初次行單側(cè)THA的患者圍術(shù)期失血量約為1 944 ml。圍術(shù)期大量、快速的出血會(huì)導(dǎo)致患者貧血；而且，術(shù)后重度貧血會(huì)導(dǎo)致關(guān)節(jié)內(nèi)感染概率增加、康復(fù)時(shí)間延長(zhǎng)，甚至?xí)Ｃ{患者的生命安全，增加患者死亡風(fēng)險(xiǎn)[12]。目前，異體輸血是治療THA圍術(shù)期貧血的常規(guī)方案。Hart等[13]分析了2011年美國(guó)骨科統(tǒng)計(jì)數(shù)據(jù)，結(jié)果提示，9 362例接受初次單側(cè)THA的患者中，接受異體輸血者占22.2%。目前，雖然異體輸血技術(shù)已有顯著提高，但仍存在醫(yī)源性感染、免疫反應(yīng)、輸血反應(yīng)、住院費(fèi)增加等風(fēng)險(xiǎn)及顧慮[14-15]。同時(shí)，我國(guó)臨床用血需求量迅速增長(zhǎng)，血液供應(yīng)緊張現(xiàn)象日益突出，部分地區(qū)甚至出現(xiàn)“血荒”[16]。因此，減少臨床用血，意義重大，不僅能保護(hù)珍貴的血液資源，而且能減少經(jīng)血液傳播的相關(guān)疾病[4-5]。

本研究在保證患者手術(shù)安全的前提下，充分調(diào)動(dòng)患者自身造血潛能，以改善THA患者圍術(shù)期的貧血狀態(tài)。促紅細(xì)胞生成素(erythropoietin，EPO)是哺乳動(dòng)物腎臟分泌的一種糖蛋白，它能夠作用于紅細(xì)胞生成的各個(gè)階段，促進(jìn)骨髓系祖細(xì)胞增殖分化，增多血液中紅細(xì)胞數(shù)量和血紅蛋白含量。rhEPO是利用基因工程技術(shù)，將人的EPO基因植入哺乳動(dòng)物的細(xì)胞內(nèi)，進(jìn)行高效表達(dá)的產(chǎn)物，它具有和促紅細(xì)胞生成素類似的生理作用，能夠提高患者的造血潛能[17]。應(yīng)用rhEPO治療期間因出現(xiàn)有效造血，鐵需求量增加，通常會(huì)出現(xiàn)血清鐵含量下降，聯(lián)合應(yīng)用蔗糖鐵能夠有效補(bǔ)充血清鐵濃度，為造血提供原料，提高rhEPO的療效[18]。蔗糖鐵注射液為多核氫氧化鐵(Ⅲ)-蔗糖復(fù)合物溶液，毒性低，幾乎無(wú)過敏反應(yīng)，且不易被腎臟清除，靜脈給藥后經(jīng)網(wǎng)狀內(nèi)皮系統(tǒng)迅速分解，與轉(zhuǎn)鐵蛋白結(jié)合，補(bǔ)充鐵儲(chǔ)備，加速紅細(xì)胞生成[19]。蔗糖鐵與口服鐵劑相比起效更快，生物利用度也更高[20]。

本研究結(jié)果顯示，術(shù)后觀察組患者Hb和RBC水平均明顯高于對(duì)照組，且兩組患者在用藥過程中均無(wú)明顯的不良反應(yīng)發(fā)生。由此可見，rhEPO聯(lián)合蔗糖鐵注射液是治療THA圍術(shù)期貧血的一種安全、有效、方便的方法，值得在臨床中推廣使用。

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Application of recombinant human erythropoietin and iron sucrose in the perioperative period of total hip replacement

WANG Bai-sheng，LIU Xin-wei，ZHANG Jing-dong，HAN Wen-feng,HE Yong,LIU Hai-li

(Department of Orthopedics,The General Hospital of Shenyang Military Command,Shenyang 110016,China)

Abstract：ObjectiveTo observe the effect of recombinant human erythropoietin(rhEPO) combined with iron sucrose in perioperative of total hip arthroplasty(THA).MethodsFrom September 2015 to March 2016,totally 97 cases of total hip arthroplasty patients treated in Department of Orthopedics,The General Hospital of Shenyang Military Command were received in this study.All cases were randomly divided into control group(48 cases) and observation group(49 cases).The patients in control group were given oral iron,dietary supplements according to their hemoglobin levels.The observation group began 3 days before surgery,to give the recombinant human erythropoietin(rhEPO) 150IU/kg subcutaneously one day,to seventh days after surgery,while the iron sucrose 100 mg intravenous infusion,3 times a week.At 1,3,5,7 days after the operation,observation was performed between the two groups of patients on hemoglobin(Hb) and the change of red blood cells(RBC).ResultsAfter operation,the Hb levels of the observation group were obvious higher than those of the control group(P<0.05),and the RBC levels of the observation group were also obvious higher than those of the control group(P<0.05).ConclusionThe effect of rhEPO combined with iron sucrose in perioperative of THA is satisfied,which can avoid the risk of allogeneic blood transfusion and ease the current tension in the blood.

Key words:Recombinant human erythropoietin;Iron sucrose;Total hip arthroplasty;Perioperative;Anemia

基金項(xiàng)目：遼寧省科學(xué)技術(shù)計(jì)劃項(xiàng)目(2015020403)

通信作者：張敬東，E-mail：zhangjingdongdr@163.com

文章編號(hào)：2095-5561(2016)03-0144-04 中圖分類號(hào)：R687

文獻(xiàn)標(biāo)志碼：A

收稿日期：2015-12-25

第一作者：王百盛(1992-)，男，遼寧大連人，醫(yī)師，碩士