甲強(qiáng)龍?jiān)趦和w外循環(huán)輔助下心臟手術(shù)中應(yīng)用價(jià)值的系統(tǒng)評(píng)價(jià)和Meta分析

謝 羚 許 燕 舒仕瑜

·論著·

甲強(qiáng)龍?jiān)趦和w外循環(huán)輔助下心臟手術(shù)中應(yīng)用價(jià)值的系統(tǒng)評(píng)價(jià)和Meta分析

謝 羚1許 燕1舒仕瑜2

目的 評(píng)估兒童體外循環(huán)輔助下心臟手術(shù)圍術(shù)期應(yīng)用甲強(qiáng)龍的價(jià)值。方法 納入體外循環(huán)輔助下行心臟手術(shù)年齡<16歲的患兒、英文RCT、試驗(yàn)組預(yù)防性應(yīng)用甲強(qiáng)龍、對(duì)照組為安慰劑或空白對(duì)照的文獻(xiàn)。檢索PubMed、Embase、Medline和 Cochrane圖書(shū)館數(shù)據(jù)庫(kù)，以PubMed為例，檢索式：methylprednisolone AND cardiopulmonary bypass OR CPB。檢索時(shí)間均為建庫(kù)至2016年5月13日。主要結(jié)局指標(biāo)為術(shù)后出院時(shí)病死率，并根據(jù)甲強(qiáng)龍給藥方式(術(shù)前靜脈給藥和術(shù)中膜肺給藥)行分層分析。采用Cochrane協(xié)作網(wǎng)推薦的偏倚風(fēng)險(xiǎn)評(píng)估工具評(píng)價(jià)文獻(xiàn)質(zhì)量。結(jié)果 系統(tǒng)檢索后6篇文獻(xiàn)中的486例體外循環(huán)輔助下心臟手術(shù)患兒進(jìn)入本文分析，其中甲強(qiáng)龍組253例，對(duì)照組233例。5篇文獻(xiàn)描述了隨機(jī)序列產(chǎn)生方法，2篇文獻(xiàn)采用了分配隱藏，6篇文獻(xiàn)均采用了盲法并描述了脫落或失訪，5篇文獻(xiàn)未選擇性報(bào)告研究結(jié)果，其他偏倚來(lái)源均為不確定。2篇靜脈給藥的文獻(xiàn)術(shù)后病死率為 9.6%(13/135)，甲強(qiáng)龍組與對(duì)照組術(shù)后病死率[1.5%(2/67)vs8.1%(11/68)]，差異有統(tǒng)計(jì)學(xué)意義(固定效應(yīng)模型，RR =0.22，95%CI：0.06～0.83，P=0.03)。次要結(jié)局指標(biāo)中體外循環(huán)(CPB )時(shí)間(固定效應(yīng)模型，MD=-10.67，95% CI：-17.82～-3.53，P=0.003)和術(shù)前靜脈給藥亞組ICU住院時(shí)間(固定效應(yīng)模型，MD=-0.72，95%CI：-1.33～-0.12，P=0.02)與對(duì)照組比較差異均有統(tǒng)計(jì)學(xué)意義。術(shù)中膜肺給藥亞組ICU住院時(shí)間以及甲強(qiáng)龍組機(jī)械通氣時(shí)間和阻斷時(shí)間與對(duì)照組比較差異均無(wú)統(tǒng)計(jì)學(xué)意義。結(jié)論 在有限證據(jù)下，兒童體外循環(huán)輔助下心臟手術(shù)圍術(shù)期預(yù)防性靜脈使用甲強(qiáng)龍可降低術(shù)后病死率，術(shù)前靜脈給藥可以縮短CPB時(shí)間和ICU住院時(shí)間。

甲強(qiáng)龍； 兒童 ； 體外循環(huán)； 心臟手術(shù)； 特異度； 系統(tǒng)評(píng)價(jià)； meta分析

在體外循環(huán)(CPB)輔助下開(kāi)胸行心臟畸形矯治仍然是目前治療先天性心臟病最主要的方法[1]。但CPB技術(shù)已被證明可以導(dǎo)致全身炎癥反應(yīng)發(fā)生[2]，主要機(jī)制是損傷血管內(nèi)皮細(xì)胞、上調(diào)黏附分子的表達(dá)、活化中性粒細(xì)胞和啟動(dòng)凝血級(jí)聯(lián)反應(yīng)[3,4]，從而導(dǎo)致患者在CPB過(guò)程中發(fā)生缺血-再灌注損傷、肺功能障礙、低心輸出量和多器官衰竭甚至死亡[5,6,7]。為減少CPB不良反應(yīng)的發(fā)生，研究人員采取了很多措施，包括術(shù)中不用CPB技術(shù)[8,9]、應(yīng)用生物相容電路及減輕系統(tǒng)反應(yīng)的藥物[10]等，其中最常應(yīng)用的是糖皮質(zhì)激素，甲強(qiáng)龍使用最廣泛。糖皮質(zhì)激素作為一種廉價(jià)的抗炎藥物，已有研究證明其可以減輕CPB后全身炎癥反應(yīng)，還可降低患者術(shù)后病死率、縮短住院時(shí)間和減少術(shù)后并發(fā)癥的發(fā)生[12,13,15,17,18,20]，但也有研究表明糖皮質(zhì)激素應(yīng)用于CPB益處不大，且不良反應(yīng)不容忽視，因此相關(guān)臨床結(jié)果飽受爭(zhēng)議[11,14,16,19]。

2011年國(guó)內(nèi)1篇Meta分析[21]對(duì)皮質(zhì)類固醇在CPB下兒童心臟手術(shù)中的作用做了評(píng)價(jià)，結(jié)果顯示圍術(shù)期應(yīng)用皮質(zhì)類固醇不能縮短患兒ICU停留時(shí)間和機(jī)械通氣時(shí)間，但可降低直腸溫度峰值；由于使用的皮質(zhì)類固醇藥物不同等原因，可能造成結(jié)果的偏倚。本文進(jìn)一步檢索了在CPB輔助下行心臟手術(shù)的兒童中應(yīng)用甲強(qiáng)龍的RCT和NRCT，慎重評(píng)價(jià)其應(yīng)用價(jià)值。

1 方法

1.1 文獻(xiàn)的納入和剔除標(biāo)準(zhǔn) ①RCT或NRCT文獻(xiàn)；②英文文獻(xiàn)；③研究對(duì)象為年齡<16歲的CPB輔助下行心臟手術(shù)的患兒；④干預(yù)措施：試驗(yàn)組CPB+甲強(qiáng)龍預(yù)防性抗炎，對(duì)照組為CPB+安慰劑或空白或其他的試驗(yàn)。剔除重復(fù)發(fā)表的文獻(xiàn)、明顯不相關(guān)文獻(xiàn)和非干預(yù)性研究文獻(xiàn)。甲強(qiáng)龍預(yù)防性抗炎是指：術(shù)前無(wú)相關(guān)炎性感染依據(jù)，為預(yù)防CPB所致炎癥反應(yīng)綜合征而應(yīng)用。

1.2 文獻(xiàn)檢索策略

1.2.1 檢索數(shù)據(jù)庫(kù)及時(shí)間 由謝羚及許燕檢索英文數(shù)據(jù)庫(kù)：PubMed、Embase、Medline和 Cochrane圖書(shū)館；檢索時(shí)間為建庫(kù)至2016年5月13日。同時(shí)回溯納入文獻(xiàn)的參考文獻(xiàn)。

1.2.2 檢索策略 英文檢索詞：“methylprednisolone”、“ cardiopulmonary bypass”、 “CPB”；以PubMed為例，檢索式：methylprednisolone AND cardiopulmonary bypass OR CPB。

1.3 結(jié)局指標(biāo) 主要結(jié)局指標(biāo)：術(shù)后病死率(即術(shù)后住院期間因各種原因的死亡)；次要結(jié)局指標(biāo)：CPB時(shí)間、ICU住院時(shí)間(患者術(shù)后轉(zhuǎn)入ICU停留時(shí)間)、阻斷時(shí)間(升主動(dòng)脈夾閉到開(kāi)放的時(shí)間)、機(jī)械通氣時(shí)間。

1.4 文獻(xiàn)質(zhì)量評(píng)價(jià) 采用Cochrane協(xié)作網(wǎng)推薦的偏倚風(fēng)險(xiǎn)評(píng)估工具(共6條)進(jìn)行，包括序列是否隨機(jī)產(chǎn)生，是否做到分配隱藏，參與者、研究者和結(jié)果評(píng)價(jià)是否運(yùn)用盲法，數(shù)據(jù)結(jié)果是否完整，是否選擇性報(bào)告結(jié)果和其他偏倚。以“高”、“低”、“不確定”作為風(fēng)險(xiǎn)評(píng)價(jià)，任意1條被評(píng)為高偏倚風(fēng)險(xiǎn)時(shí)，則該文獻(xiàn)被認(rèn)為存在高偏倚風(fēng)險(xiǎn)；每條都被評(píng)為低風(fēng)險(xiǎn)時(shí)，則該文獻(xiàn)被認(rèn)為偏倚風(fēng)險(xiǎn)低；余認(rèn)為偏倚風(fēng)險(xiǎn)不確定。

1.5 數(shù)據(jù)提取原則 由謝羚和許燕分別獨(dú)立按設(shè)計(jì)表格提取資料，當(dāng)意見(jiàn)不一致時(shí)協(xié)商，仍無(wú)法確定時(shí)由舒仕瑜決定。

1.6 統(tǒng)計(jì)學(xué)分析 采用 RevMan 5.3分析軟件，將資料進(jìn)行定量綜合。二分類變量使用相對(duì)危險(xiǎn)度(RR)及其相應(yīng)的95%CI來(lái)評(píng)價(jià)，連續(xù)型變量當(dāng)數(shù)據(jù)單位相同時(shí)，使用加權(quán)均數(shù)差(WMD)及其相應(yīng)的95%CI評(píng)價(jià)，當(dāng)數(shù)據(jù)單位不相同時(shí)，使用標(biāo)準(zhǔn)均數(shù)差(SMD)及其相應(yīng)的95%CI評(píng)價(jià)。多組比較時(shí)根據(jù) Cochrane手冊(cè)的指導(dǎo)將各組數(shù)據(jù)合并為可比較的干預(yù)組與對(duì)照組。 使用I2檢驗(yàn)來(lái)評(píng)價(jià)數(shù)據(jù)的異質(zhì)性，當(dāng)I2≥50%時(shí)，使用隨機(jī)效應(yīng)模型，當(dāng)I2<50%時(shí)，使用固定效應(yīng)模型。

2 結(jié)果

2.1 文獻(xiàn)檢索過(guò)程 根據(jù)本文文獻(xiàn)檢索策略，共檢出相關(guān)文獻(xiàn)518篇，PubMed 155篇，Embase 116篇，Medline 149篇，Cochrane 98篇，符合本文剔除標(biāo)準(zhǔn)文獻(xiàn)512篇， 6篇文獻(xiàn)[12,13,14,20,22,23]486例CPB輔助下心臟手術(shù)患兒進(jìn)入本文分析，納入分析文獻(xiàn)的參考文獻(xiàn)中未回溯到相關(guān)文獻(xiàn)，其中甲強(qiáng)龍組253例，對(duì)照組233例。

2.2 文獻(xiàn)特征 表1顯示納入的6篇文獻(xiàn)的基本特征，文獻(xiàn)[14]和[20]由芬蘭同一研究組在不同時(shí)間完成。文獻(xiàn)[20]甲強(qiáng)龍組中分為術(shù)前靜脈給藥亞組和術(shù)中膜肺給藥亞組，與同一對(duì)照組比較。

2.3 質(zhì)量評(píng)價(jià) 圖1顯示，4篇文獻(xiàn)[12,16,18,22]描述了隨機(jī)序列產(chǎn)生方法，2篇文獻(xiàn)[16,18]采用了分配隱藏，5篇文獻(xiàn)對(duì)試驗(yàn)實(shí)施者施盲[12,16,18,22,23]，5篇文獻(xiàn)[11,12,16,18,23]未選擇性報(bào)告研究結(jié)果，6篇文獻(xiàn)均描述了脫落或失訪，其他偏倚來(lái)源均為不確定。

圖1 納入文獻(xiàn)偏倚風(fēng)險(xiǎn)

注 1：隨機(jī)序列產(chǎn)生(選擇偏倚)；2：分配隱藏(選擇偏倚)；3：實(shí)施者和參與者雙盲(實(shí)施偏倚)；4： 結(jié)局評(píng)估中的盲法 (測(cè)量偏倚)；5： 不全結(jié)局?jǐn)?shù)據(jù)(失訪偏倚)；6：選擇性報(bào)道(發(fā)表偏倚)；7： 其他偏倚

表1 納入研究的基本特征

注 T：甲強(qiáng)龍組；C：對(duì)照組；ASD：房間隔缺損；VSD：室間隔缺損；TOF：法洛四聯(lián)征；AVSD：房室間隔缺損；CPB：體外循環(huán)；阻斷時(shí)間：升主動(dòng)脈夾閉到開(kāi)放的時(shí)間

2.4 Meta分析結(jié)果

2.4.1 主要結(jié)局指標(biāo) 圖2顯示，2篇文獻(xiàn)報(bào)告了術(shù)后病死率[12，18]為 9.6%(13/135)，甲強(qiáng)龍組術(shù)后病死率1.5%(2/67)，對(duì)照組術(shù)后病死率8.1%(11/68)。文獻(xiàn)[12]和[18]均為靜脈給藥，文獻(xiàn)[12]為術(shù)前、術(shù)中和術(shù)后同時(shí)給藥6次，文獻(xiàn)[18]為術(shù)前給藥1次。 文獻(xiàn)間具同質(zhì)性，固定效應(yīng)模型Meta分析結(jié)果顯示，兩組術(shù)后病死率差異有統(tǒng)計(jì)學(xué)意義，RR=0.22，95%CI：0.06～0.83，P=0.003。

圖2 甲強(qiáng)龍組與對(duì)照組術(shù)后病死率比較Meta分析

2.4.2 次要結(jié)局指標(biāo)

2.4.2.1 CPB 時(shí)間 圖3顯示，5篇文獻(xiàn)[11，16，18,22,23]報(bào)道了CPB 時(shí)間。文獻(xiàn)間具同質(zhì)性，固定效應(yīng)模型Meta分析結(jié)果顯示，兩組CPB 時(shí)間差異有統(tǒng)計(jì)學(xué)意義，MD=-10.67，95% CI：-17.82～-3.53，P=0.003。其中2篇文獻(xiàn)[16,23]描述術(shù)中膜肺給藥，3篇文獻(xiàn)[11,16,18]描述術(shù)前靜脈給藥，1篇文獻(xiàn)[22]描述術(shù)前及術(shù)后聯(lián)合靜脈給藥。術(shù)前靜脈給藥亞組CPB時(shí)間與對(duì)照組差異有統(tǒng)計(jì)學(xué)意義，固定效應(yīng)模型合并MD=-13.33，95%CI：-23.46～-3.19，P=0.01。術(shù)中膜肺給藥亞組CPB時(shí)間與對(duì)照組差異無(wú)統(tǒng)計(jì)學(xué)意義，固定效應(yīng)模型合并MD=-7.94，95%CI：-18.07～2.19，P=0.12。

圖3 甲強(qiáng)龍組與對(duì)照組CPB時(shí)間比較Meta分析

2.4.2.2 ICU住院時(shí)間 圖4顯示， 4篇文獻(xiàn)報(bào)道了ICU住院時(shí)間[11,16，18,23]。文獻(xiàn)間具異質(zhì)性，隨機(jī)效應(yīng)模型Meta分析結(jié)果顯示，兩組ICU住院時(shí)間差異無(wú)統(tǒng)計(jì)學(xué)意義，SMD=-0.04，95% CI：-0.49～0.42，P=0.88。其中2篇文獻(xiàn)[16,23]描述術(shù)中膜肺給藥，3篇文獻(xiàn)[11,16,18]描述術(shù)前靜脈給藥。根據(jù)給藥方式不同行亞組分析，術(shù)前靜脈給藥亞組ICU住院時(shí)間與對(duì)照組差異有統(tǒng)計(jì)學(xué)意義，固定效應(yīng)模型合并MD=-0.72，95%CI：-1.33～-0.12，P=0.02。術(shù)中膜肺給藥亞組ICU住院時(shí)間與對(duì)照組差異無(wú)統(tǒng)計(jì)學(xué)意義，固定效應(yīng)模型合并 SMD=0.27，95%CI：-0.24～-0.78，P=0.29。 需要說(shuō)明的是，文獻(xiàn)[16]同時(shí)做了術(shù)前靜脈應(yīng)用甲強(qiáng)龍與安慰劑、術(shù)中膜肺應(yīng)用甲強(qiáng)龍與安慰劑的隨機(jī)對(duì)照試驗(yàn)，故圖中顯示2次。

圖4 甲強(qiáng)龍組與對(duì)照組ICU住院時(shí)間比較Meta分析

2.4.2.3 機(jī)械通氣時(shí)間 圖5顯示，4篇文獻(xiàn)[11,16,18,23]報(bào)道了機(jī)械通氣時(shí)間。文獻(xiàn)間具異質(zhì)性，隨機(jī)效應(yīng)模型Meta分析結(jié)果顯示兩組機(jī)械通氣時(shí)間差異無(wú)統(tǒng)計(jì)學(xué)意義，SMD=-0.10，95% CI：-1.01～1.21，P=0.86。術(shù)前靜脈給藥亞組和術(shù)中膜肺給藥亞組機(jī)械通氣時(shí)間與對(duì)照組差異均無(wú)統(tǒng)計(jì)學(xué)意義，隨機(jī)效應(yīng)模型合并SMD分別為-0.66和1.36，95%CI分別為-1.48～0.16和-1.36～4.07，P>0.05。

圖5 甲強(qiáng)龍組與對(duì)照組機(jī)械通氣時(shí)間比較Meta分析

2.4.2.4 阻斷時(shí)間 圖6顯示，4篇文獻(xiàn)[11,16,18,23]報(bào)道了阻斷時(shí)間。文獻(xiàn)間具同質(zhì)性，固定效應(yīng)模型Meta分析結(jié)果顯示兩組阻斷時(shí)間差異無(wú)統(tǒng)計(jì)學(xué)意義，MD=-4.64，95%CI：-11.21～1.94，P=0.17。

圖6 甲強(qiáng)龍組與對(duì)照組阻斷時(shí)間比較Meta分析

3 討論

本Meta分析納入6篇文獻(xiàn)總體質(zhì)量較好，結(jié)果顯示，在兒童CPB輔助下心臟手術(shù)圍術(shù)期預(yù)防性使用甲強(qiáng)龍可以降低患兒的術(shù)后病死率，術(shù)前靜脈給藥可以縮短CPB時(shí)間和ICU住院時(shí)間。

甲強(qiáng)龍是一種合成的抗炎作用很強(qiáng)的短效糖皮質(zhì)激素，能通過(guò)擴(kuò)散透過(guò)細(xì)胞膜，并與特殊的細(xì)胞內(nèi)受體相結(jié)合，進(jìn)入細(xì)胞核內(nèi)與 DNA 結(jié)合，并啟動(dòng) mRNA 的轉(zhuǎn)錄和 翻譯，繼而合成各種酶蛋白。這些酶能阻止各類炎性介質(zhì)的釋放，阻止CPB時(shí)氧自由基對(duì)組織細(xì)胞的氧化損傷，對(duì)肺組織及其他組織起到一定的保護(hù)作用，從而減輕CPB過(guò)程中全身炎癥反應(yīng)[2,17]。

早在21世紀(jì)初，研究人員就已經(jīng)開(kāi)始關(guān)注糖皮質(zhì)激素治療在CPB所致全身炎癥反應(yīng)的作用，并進(jìn)行了相關(guān)的RCT[24,25]，證明了糖皮質(zhì)激素在藥物品種不同、劑量不同和給藥時(shí)間不同的情況下均可減少炎癥介質(zhì)的產(chǎn)生，改變患兒的血流動(dòng)力學(xué)效應(yīng)，最終減少全身炎癥反應(yīng)的發(fā)生。然而，最近有Meta分析或大樣本觀察性研究表明，預(yù)防性使用糖皮質(zhì)激素并沒(méi)有益處，反而會(huì)增加低風(fēng)險(xiǎn)患兒的術(shù)后并發(fā)癥的發(fā)生率[13,14,20,25-27]。

對(duì)于術(shù)前應(yīng)用甲強(qiáng)龍是否優(yōu)于術(shù)中，靜脈使用是否優(yōu)于膜肺給藥，目前認(rèn)識(shí)不一致。Keski-Nisula等[16]的研究對(duì)比了術(shù)前麻醉誘導(dǎo)時(shí)應(yīng)用甲強(qiáng)龍與術(shù)中CPB時(shí)應(yīng)用甲強(qiáng)龍的效果，提示術(shù)前麻醉誘導(dǎo)時(shí)應(yīng)用甲強(qiáng)龍抗炎效果更優(yōu)。本文通過(guò)對(duì)術(shù)前靜脈給藥(術(shù)前靜脈亞組)和術(shù)中膜肺給藥(術(shù)中膜肺亞組)行分層分析，結(jié)論與Keski-Nisula等的研究相似，術(shù)前靜脈給藥方式可能優(yōu)于術(shù)中膜肺給藥，但鑒于文獻(xiàn)數(shù)量和樣本量有限，仍需要兩種給藥方式的RCT予以驗(yàn)證。

關(guān)于甲強(qiáng)龍的劑量及使用頻率目前亦無(wú)明確結(jié)論。Soltani等[28]的研究對(duì)比了術(shù)前應(yīng)用單一劑量甲強(qiáng)龍與術(shù)前、術(shù)中聯(lián)合重復(fù)應(yīng)用甲強(qiáng)龍的效果，提示二者的臨床結(jié)果并無(wú)差異。Schroeder等[24]的研究證明聯(lián)合應(yīng)用甲強(qiáng)龍與術(shù)中單一劑量甲強(qiáng)龍相比，能提高患兒的氧輸送，減輕心肌損害和減少全身炎癥介質(zhì)的釋放。目前仍以30 mg·kg-1劑量為標(biāo)準(zhǔn)。

在有限證據(jù)下，兒童CPB輔助下心臟手術(shù)圍術(shù)期預(yù)防性靜脈使用甲強(qiáng)龍可降低術(shù)后病死率，術(shù)前靜脈給藥可以縮短CPB時(shí)間和ICU住院時(shí)間。

[1]Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics-2012 update: a report from the American Heart Association. Circulation, 2012, 125(1): e2-e220

[2]Pasquali SK, Hall M, Li JS, et al. Corticosteroids and outcome in children undergoing congenital heart surgery: analysis of the Pediatric Health Information Systems database. Circulation, 2010, 122(21): 2123-2130

[3]Kirklin JK, Westaby S, Blackstone EH, et al. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg, 1983, 86(6): 845-857

[4]Lefer AM, Campbell B, Scalia R, et al. Synergism between platelets and neutrophils in provoking cardiac dysfunction after ischemia and reperfusion. Circulation, 1998, 98(13): 1322-1328

[5]Haddad R, El-Hassan D, Araj A, et al. Some inflammation-related parameters in patients following normo- and hypothermic cardio-pulmonary bypass. Immunopharmacol Immunotoxicol, 2001, 23(2): 291-302

[6]De Greef KE, Ysebaert DK, Ghielli M. Neutrophils and acute ischemia-reperfusion injury. J Nephrol, 1998, 11(3): 110-122

[7]Holmes JH, Connolly NC, Paull DL, et al. Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes. Inflamm Res, 2002, 51(12): 579-586

[8] Ascione R, Lloyd CT, Underwood MJ, et al. Inflammatory response after coronary revascularization with or without cardiopulmonary bypass. Ann Thorac Surg, 2000, 69(4): 1198-1204

[9] Gulielmos V, Menschikowski M, Dill H, et al. Interleukin-1, interleukin-6 and myocardial enzyme response after coronary artery bypass grafting-a prospective randomized comparison of the conventional and three minimally invasive surgical techniques. Eur J Cardiothorac Surg, 2000, 18(5): 594-601

[10]Rubens FD, Mesana T. The inflammatory response to cardiopulmonary bypass: a therapeutic overview. Perfusion, 2004, 19(Suppl 1): S5-S12

[11] Poyrazoglu HH, Duman Z, Demir, et al. Investigating the impacts of preoperative steroid treatment on tumor necrosis factor-alpha and duration of extubation time underwent ventricular septal defect surgery. Balkan Med J, 2016, 33: 158-163

[12]Toledo-Pereyra LH, Lin CY, Kundler H, et al. Steroids in heart surgery: A clinical double-blind and randomized study. Am Surg, 1980, 46: 155-160

[13]Graham EM, Atz AM, Butts RJ, et al. Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery: Results from a randomized trial. J Thorac Cardiovasc Surg, 2011, 142: 1523-1529

[14]Pasquali SK, Hall M, Li JS, et al. Corticosteroids and outcome in children undergoing congenital heart surgery: analysis of the Pediatric Health Information Systems database. Circulation, 2010, 122(21): 2123-2130

[15]Gessler P, Hohl V, Carrel T, et al. Administration of steroids in pediatric cardiac surgery: Impact on clinical outcome and systemic inflammatory response. Pediatr Cardiol, 2005, 26(5): 595-600

[16] Keski-Nisula J, Suominen PK, Olkkola KT, et al. Effect of timing and route of methylprednisolone administration during pediatric cardiac surgical procedures. Ann Thorac Surg, 2015, 99(1): 180-185

[17] Chaney MA, Durazo-Arvizu RA, Nikolov MP, et al. Methylprednisolone does not benefit patients undergoing coronary artery bypass grafting and early tracheal extubation. J Thorac Cardiovasc Surg, 2001, 121(3): 561-569

[18]Keski-Nisula J, Pesonen E, Olkkola KT, et al. Methylprednisolone in neonatal cardiac surgery: Reduced inflammation without improved clinical outcome. Ann Thorac Surg, 2013, 95: 2126-2132

[19]Mastropietro CW, Barrett R, Davalos MC, et al. Cumulative corticosteroid exposure and infection risk after complex pediatric cardiac surgery. Ann Thorac Surg, 2013, 95: 2133-2139

[20]Robertson-Malt S, Afrane B, Elbarbary M. Prophylactic steroids for pediatric open heart surgery. Cochrane Database Syst Rev, 2007, (4): CD005550

[21]賈鶴齡, 張彬, 張斌飛, 等. 皮質(zhì)類固醇在體外循環(huán)下小兒心臟手術(shù)中的作用的meta分析. 蘭州大學(xué)學(xué)報(bào), 2011, 37(4): 50-53

[22] Mott AR, Fraser CD Jr, Kusnoor AV, et al. The effect of short-term prophylactic methylprednisolone on the incidence and severity of postpericardiotomy syndrome in children undergoing cardiac surgery with cardiopulmonary bypass. J Am Coll Cardiol, 2001, 37(6): 1700-1706

[23]Liu JP, Ji BY, Long C, et al. Comparative effectiveness of methylprednisolone and zero-balance ultrafiltration on inflammatory response after pediatric cardiopulmonary bypass. Artif Organs, 2007, 31(7): 571-575

[24]Schroeder VA, Pearl JM, Schwartz SM, et al. Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression. Circulation, 2003, 107(22): 2823-2828

[25]Graham EM, Atz AM, McHugh KE, et al: Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates: Results from a randomized trial. J Thorac Cardiovasc Surg 2014, 147(3): 902-908

[26]Pasquali SK, Li JS, He X, et al: Perioperative methylprednisolone and outcome in neonates undergoing heart surgery. Pediatrics, 2012, 129(2): e385-e391

[27] Ando M, Park IS, Wada N, et al. Steroid supplementation: a legitimate pharmacotherapy after neonatal open heart surgery. Ann Thorac Surg, 2005, 80(5): 1672-1678

[28]Soltani G, Abbasi Tashnizi M, Moeinipour AA, et al. Comparing the effect of preoperative administration of methylprednisolone and its administration before and during surgery on the clinical outcome in pediatric open heart surgeries. Iranian Red Crescent Medical Journal, 2013, 15(6): 483-487

(本文編輯：張崇凡，孫晉楓)

Thevalueofmethylprednisoloneusedinchildrenundergoingcardiacsurgerywithcardiopulmonarybypass:asystematicreviewandmeta-analysis

XIELing1，XUYan1，SHUShi-yu2

(1Children'sHospital,ChongqingMedicalUniversity，Chongqing400362,China；2Anesthesiologydepartment,Children'sHospital,FudanUniversity，Shanghai201102,China)

Corresponding Author：SHU Shi-yu，E-mail:shushiyu@hotmail.com

ObjectiveTo evaluate the effects of perioperative administration of methylprednisolone in pediatric patients undergoing cardiac surgery together with cardiopulmonary bypass.MethodsRandomized controlled trials published in English language involving pediatric patients aged under 16 years undergoing cardiac surgery together with cardiopulmonary bypass, which prophylactic perioperative methylprednisolone administrated during cardiac surgery was compared with placebo or blank control were included.The PubMed, Embase, Medline,and the Cochrane Library were searched systematically up to May 2016. The search strategy was "methylprednisolone" AND "cardiopulmonary bypass" OR "CPB". The primary outcome to evaluate the efficacy of methylprednisolone in pediatric cardiac surgery with cardiopulmonary bypass was all-cause in-hospital mortality. The meta-analysis was performed by RevMan 5.3 software. A subgroup analysis about delivery method was made between intravenous administration before surgery (subgroup A) and CPB circuit in CPB prime(subgroup B)． ResultsSix RCTs with 486 patients were included into this meta-analysis, including 253 patients with methylprednisolone and 233 patients with placebo or blank control. Five RCTs reported the information of random sequence generation, 2 RCTs reported adequate information about allocation concealment. All of the included RCTs reported blinding of outcome assessment and described off or lost, 5 RCTs didn't report selective results, other bias were uncertain. Compared with placebo patients, methylprednisolone administration was associated with significant reduction of postoperative mortality (RR=0.22, 95% CI: 0.06 to 0.83,P= 0.03). The results of meta-analysis showed that the CPB time was decreased in experimental groups (MD=-10.67，95% CI：-17.82 to -3.53，P=0.003)，and similar trend was found in subgroup A，the MD(95%CI) was -0.72 (95%CI: -1.33 to -0.12,P=0.02)．There was no relation with decreased cross-clamp time, mechanical ventilation time and length of ICU stay in subgroup B.ConclusionUnder the limited evidence, the delivery method of intravenous administration before surgery may be better than CPB circuit in CPB prime to decrease ICU stay and CPB time.

Methylprednisolone; Children; Cardiopulmonary bypass; Cardiac surgery; Specificity; Systematic review; Meta-analysis

1 重慶醫(yī)科大學(xué)附屬兒童醫(yī)院麻醉科 重慶，400362；2復(fù)旦大學(xué)附屬兒科醫(yī)院麻醉科 上海，201102

舒仕瑜，E-mail: shushiyu@hotmail.com

10.3969/j.issn.1673-5501.2016.06.004

2016-11-06

2016-12-18)