趙紅巖，苗志林，陶貴周，劉明新，張占修，楊 健，馮 豐，楊新斌，侯 平，陳 韋，李占全*

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國(guó)產(chǎn)碘克沙醇對(duì)老年冠心病患者腎功能影響的安全性研究

趙紅巖1，苗志林1，陶貴周2，劉明新2，張占修3，楊 健3，馮 豐4，楊新斌4，侯 平5，陳 韋5，李占全1*

（1遼寧省人民醫(yī)院心內(nèi)科，沈陽(yáng) 110016；2遼寧醫(yī)學(xué)院附屬第一醫(yī)院心內(nèi)科，錦州 121001；3解放軍第313醫(yī)院心內(nèi)科，葫蘆島 125001；4沈陽(yáng)市第一人民醫(yī)院心內(nèi)科，沈陽(yáng) 110041；5遼寧省中醫(yī)藥大學(xué)附屬醫(yī)院心內(nèi)科，沈陽(yáng) 110033）

評(píng)價(jià)國(guó)產(chǎn)碘克沙醇注射液對(duì)進(jìn)行經(jīng)皮冠狀動(dòng)脈介入治療（PCI）的老年冠心病患者腎功能的影響。采用隨機(jī)分組、單盲設(shè)計(jì)、陽(yáng)性對(duì)照的多中心研究。于2013年7月至2014年3月在遼寧省5家醫(yī)院選擇60～75歲、擬行PCI的患者88例，隨機(jī)分為試驗(yàn)組（應(yīng)用江蘇恒瑞醫(yī)藥股份有限公司生產(chǎn)的碘克沙醇注射液，44例）與對(duì)照組[應(yīng)用通用電氣藥業(yè)有限公司生產(chǎn)的威視派克（碘克沙醇商品名），44例]。記錄兩組術(shù)前年齡、性別、體質(zhì)量指數(shù)（BMI）及腎功能等基本臨床資料，術(shù)后48h檢測(cè)腎功能，從而比較兩者對(duì)老年冠心病患者腎功能的影響有無(wú)差別。兩組共入選88例患者，試驗(yàn)組與對(duì)照組均為44例。88例患者均順利完成冠狀動(dòng)脈造影與PCI，成功率100%。兩組年齡、BMI等基本臨床資料無(wú)統(tǒng)計(jì)學(xué)差異（＞0.05）。兩組PCI前后腎功能指標(biāo)相比均無(wú)統(tǒng)計(jì)學(xué)差異（＞0.05），兩組分別有1例患者術(shù)后當(dāng)天出現(xiàn)惡心嘔吐，于手術(shù)次日恢復(fù)正常；兩組均未發(fā)生對(duì)比劑誘發(fā)性急性腎損傷及其他不良反應(yīng)。國(guó)產(chǎn)碘克沙醇用于行PCI的老年冠心病患者是安全的。

碘克沙醇；經(jīng)皮冠狀動(dòng)脈介入治療；對(duì)比劑誘發(fā)性急性腎損傷；老年人

近年來(lái)隨著我國(guó)心血管造影和經(jīng)皮冠狀動(dòng)脈介入治療（percutaneous coronary intervention，PCI）數(shù)量的逐年增長(zhǎng)，含碘對(duì)比劑的應(yīng)用日益廣泛，其不良反應(yīng)尤其是對(duì)比劑誘發(fā)性急性腎損傷（contrast-induced acute kidney injury，CI-AKI）[1,2]日益受到重視。腎小球?yàn)V過(guò)率隨年齡增長(zhǎng)而降低，故老年人應(yīng)用對(duì)比劑的風(fēng)險(xiǎn)更高[3]。碘克沙醇（iodixanol）因?yàn)榱己玫陌踩?，被?guó)內(nèi)外指南[4?7]推薦選用。為評(píng)價(jià)國(guó)產(chǎn)碘克沙醇注射液對(duì)老年P(guān)CI患者腎功能的影響，遼寧省5家醫(yī)院以通用電氣藥業(yè)（上海）有限公司生產(chǎn)的商品名為威視派克（Visipaque）的碘克沙醇為對(duì)照，進(jìn)行了前瞻性的多中心單盲隨機(jī)對(duì)照臨床研究?，F(xiàn)將該研究報(bào)道如下。

1 對(duì)象與方法

本研究經(jīng)遼寧省人民醫(yī)院倫理委員會(huì)批準(zhǔn)，由遼寧省人民醫(yī)院、遼寧醫(yī)學(xué)院附屬第一醫(yī)院、解放軍第313醫(yī)院、沈陽(yáng)市第一人民醫(yī)院及遼寧省中醫(yī)藥大學(xué)附屬醫(yī)院的心內(nèi)科，于2013年7月至2014年3月協(xié)作完成。入選患者均簽署知情同意書(shū)。

1.1 研究對(duì)象入選標(biāo)準(zhǔn)

（1）60～75周歲冠心病患者88例，男女不限；（2）擬行PCI；（3）簽署知情同意書(shū)。

1.2 排除標(biāo)準(zhǔn)

（1）受試者既往對(duì)碘對(duì)比劑及含碘食物有嚴(yán)重不良反應(yīng)；（2）既往甲亢病史者；（3）有腎功能障礙，血清肌酐水平≥3mg/dl（265.2μmol/L）；（4）3個(gè)月內(nèi)發(fā)生過(guò)急性腎衰竭和（或）接受過(guò)血液透析治療患者。（5）接受過(guò)腎移植手術(shù)的患者；（6）嚴(yán)重肝功能不全患者[丙氨酸氨基轉(zhuǎn)移酶和（或）天冬氨酸氨基轉(zhuǎn)移酶≥正常參考值上限2倍]；（7）受試者不能中斷服用鹽酸二甲雙胍或包含鹽酸二甲雙胍的藥品；（8）有急性活動(dòng)性出血；（9）發(fā)熱，體溫≥38℃；（10）嚴(yán)重血液系統(tǒng)疾病患者；（11）術(shù)前14d內(nèi)接受過(guò)碘對(duì)比劑的患者；（12）預(yù)計(jì)術(shù)后7d內(nèi)需要再次接受對(duì)比劑的患者；（13）有證據(jù)顯示受試者臨床狀況不穩(wěn)定，包括：急性心肌梗死（2周之內(nèi)）；心源性休克；充血性心力衰竭或急性肺水腫；腦卒中（3個(gè)月內(nèi)）；（14）既往冠狀動(dòng)脈造影顯示為慢性完全閉塞病變、三支彌漫性病變、左主干病變等估計(jì)對(duì)比劑用量≥400ml或（和）PCI手術(shù)風(fēng)險(xiǎn)較高的患者；（15）近3個(gè)月參加過(guò)其他臨床研究；（16）不具法律能力或法律能力受限者；（17）研究者認(rèn)為不合適參加該臨床研究的任何情況。

1.3 方法

患者入選后隨機(jī)分為試驗(yàn)組（44例）與對(duì)照組（44例）。試驗(yàn)組應(yīng)用江蘇恒瑞醫(yī)藥股份有限公司生產(chǎn)的碘克沙醇注射液，規(guī)格為100ml∶65.2g（100ml∶32g I）/瓶，批準(zhǔn)文號(hào)為國(guó)藥準(zhǔn)字H20103675；對(duì)照組應(yīng)用通用電氣藥業(yè)（上海）有限公司生產(chǎn)的威視派克，規(guī)格為32g（I）/100ml/瓶，批準(zhǔn)文號(hào)為國(guó)藥準(zhǔn)字J20050104。常規(guī)進(jìn)行冠狀動(dòng)脈造影與PCI，應(yīng)用阿司匹林、氯吡格雷、他汀類調(diào)脂藥以及手術(shù)前后生理鹽水進(jìn)行水化等治療。術(shù)后隨訪1周。

1.4 觀察指標(biāo)

記錄患者的年齡、性別、身高、體質(zhì)量、生命體征、伴隨疾病、對(duì)比劑用量、術(shù)前血清肌酐（serum creatinine，SCr）與尿素氮（blood urea nitrogen，BUN）、術(shù)后48h SCr與BUN（若升高，則術(shù)后7d復(fù)查）、術(shù)中術(shù)后有無(wú)嚴(yán)重心腦血管事件及對(duì)比劑引起的不良反應(yīng)（包括CI-AKI等）。CI-AKI定義為48h內(nèi)SCr水平升高＞0.3mg/dl或7d內(nèi)升高＞50%。計(jì)算體質(zhì)量指數(shù)（body mass index，BMI）、估測(cè)腎小球?yàn)V過(guò)率（estimated glomerular filtration rate，eGFR）以及術(shù)后eGFR的減少值。eGFR[ml/（min·1.73m2）]＝175×SCr（mg/dl）-1.234×年齡-0.179×（0.79女性）[8]；術(shù)后eGFR的減少值[ml/（min·1.73m2）]＝術(shù)前eGFR-術(shù)后eGFR。

1.5 統(tǒng)計(jì)學(xué)處理

采用SPSS13.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)學(xué)分析。計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差表示，兩組均數(shù)比較采用檢驗(yàn)；計(jì)數(shù)資料以例數(shù)或所占百分比表示，組間率的比較采用2檢驗(yàn)。所有的統(tǒng)計(jì)檢驗(yàn)均采用雙側(cè)檢驗(yàn)，＜0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié) 果

2.1 基本臨床資料

88例患者均順利完成冠狀動(dòng)脈造影與PCI（成功率100%），隨訪期間均無(wú)死亡、腦卒中、急性心肌梗死、再次血運(yùn)重建等嚴(yán)重心腦血管事件發(fā)生。兩組基本臨床資料比較，差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05；表1）。

2.2 PCI前后腎功能情況

兩組PCI前后腎功能指標(biāo)相比均無(wú)統(tǒng)計(jì)學(xué)差異（＞0.05；表2），兩組分別有1例患者術(shù)后當(dāng)天出現(xiàn)惡心、嘔吐，于手術(shù)次日恢復(fù)正常；兩組均未發(fā)生CI-AKI及其他不良反應(yīng)。

表1 兩組基本臨床資料表

BMI: body mass index

表2 兩組PCI前后腎功能情況表

PCI: percutaneous coronary intervention; eGFR: estimated glomerular filtration rate; SCr: serum creatinine; BUN: blood urea nitrogen

3 討 論

老年冠心病患者進(jìn)行PCI治療的數(shù)量逐年增多，而老年患者冠狀動(dòng)脈及全身動(dòng)脈病理改變較中青年患者更加嚴(yán)重，冠狀動(dòng)脈多存在多支、紆曲和鈣化等復(fù)雜病變，PCI術(shù)中對(duì)比劑需求量相對(duì)增多；老年患者腎小球?yàn)V過(guò)率及心臟儲(chǔ)備功能下降，而且合并高血壓病、糖尿病、心功能不全的概率增高（本研究中排除了心力衰竭，入選患者合并高血壓病、糖尿病的比例仍分別超過(guò)40%與10%），腎臟對(duì)對(duì)比劑不良反應(yīng)的代償能力降低。以上因素導(dǎo)致老年患者發(fā)生腎功能損害的風(fēng)險(xiǎn)及其危害性增加[7]。

基礎(chǔ)腎功能損害是預(yù)測(cè)接受碘對(duì)比劑檢查的患者發(fā)生CI-AKI的最重要的標(biāo)志，因此老年患者PCI術(shù)前一定要評(píng)價(jià)腎功能狀態(tài)，計(jì)算eGFR而不是單純依據(jù)血肌酐水平判斷。若eGFR＜60ml/（min·1.73m2），則視為CI-AKI的高?；颊遊9?11]。若老年患者病情需行PCI治療，在應(yīng)用他汀類調(diào)脂藥物[12]，盡量減少對(duì)比劑用量，及術(shù)前術(shù)后積極有效水化治療的同時(shí)，選擇循證醫(yī)學(xué)證實(shí)安全的對(duì)比劑是非常重要的[13,14]。等滲對(duì)比劑碘克沙醇為非離子型二聚體，其滲透壓與血漿滲透壓相等[15]，上市后經(jīng)眾多臨床研究證實(shí)其安全性良好，故被國(guó)內(nèi)外眾多指南所推薦[4?7]。

本研究為前瞻性多中心單盲隨機(jī)對(duì)照臨床研究，結(jié)果顯示在老年冠心病患者進(jìn)行PCI時(shí)應(yīng)用國(guó)產(chǎn)碘克沙醇注射液與威視派克均無(wú)CI-AKI等嚴(yán)重不良反應(yīng)，其他不良反應(yīng)輕微而發(fā)生率相近。因此，國(guó)產(chǎn)的碘克沙醇注射液與威視派克相比同樣安全，可用于老年冠心病患者的PCI治療，因其價(jià)格更加便宜，值得在臨床工作中推廣。但本研究樣本例數(shù)偏小，更加確切的結(jié)論有待更大規(guī)模的前瞻性隨機(jī)對(duì)照研究來(lái)證實(shí)。

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（編輯: 李菁竹）

Nephrotoxic effects of domestic iodixanol injection in old patients with coronary heart disease

ZHAO Hong-Yan1, MIAO Zhi-Lin1, TAO Gui-Zhou2, LIU Ming-Xin2; ZHANG Zhan-Xiu3, YANG Jian3, FENG Feng4, YANG Xin-Bin4; HOU Ping5, CHEN Wei5, LI Zhan-Quan1*

(1Department of Cardiology, Liaoning Provincial People’s Hospital, Shenyang 110016, China;2Department of Cardiology, the First Affiliated Hospital, Liaoning Medical College, Jinzhou 121001, China;3Department of Cardiology, Chinese PLA Hospital No.313, Huludao 125001, China;4Department of Cardiology, Shenyang First People’s Hospital, Shenyang 110041, China;5Department of Cardiology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110033, China)

To evaluate the nephrotoxic effects of domestic iodixanol injection in the elderly patients with coronary heart disease (CHD).A multicenter, single blind, randomized controlled clinic trial was prospectively carried out in 5 hospitals in Liaoning Province from July 2013 to March 2014. Eighty-eight patients of 60 to 75 years old with CHD undergoing percutaneous coronary intervention (PCI) were divided into 2 groups: experimental group (domestic iodixanol injection group,＝44) and control group [Visipaque (trade name of iodixanol) group,＝44]. The clinical information including age, gender, body mass index (BMI), serum creatinine (SCr) and blood urea nitrogen (BUN) was recorded before PCI. Their SCr and BUN were determined in 48 h after PCI for renal function in the patients of the 2 groups.All of them underwent PCI smoothly, with a successful rate of 100%. There was no significant difference in the age, gender, BMI, SCr and BUN between the 2 groups before PCI (＞0.05). No difference was found in the renal function in the 2 groups before and after PCI (＞0.05). One patient of each group had nausea and vomiting respectively just in the day after operation, and recovered on the next day. None of patient had contrast-induced acute kidney injury or other adverse reactions.Domestic iodixanol injection is safe for old patients with CHD underwent PCI.

iodixanol; percutaneous coronary intervention; contrast-induced acute kidney injury; aged

R654.33; R541.4; R592

A

10.3724/SP.J.1264.2014.000160

2014?05?18;

2014?07?07

李占全, E-mail: lzqlr@medmail.com.cn