術(shù)中目標(biāo)引導(dǎo)液體治療對(duì)高危老年患者術(shù)后預(yù)后的影響

徐 婧，張丹鳳，朱賽楠，王東信*

?

術(shù)中目標(biāo)引導(dǎo)液體治療對(duì)高危老年患者術(shù)后預(yù)后的影響

徐 婧1，張丹鳳1，朱賽楠2，王東信1*

（北京大學(xué)第一醫(yī)院：1麻醉科，2醫(yī)學(xué)統(tǒng)計(jì)室，北京 100034）

觀察基于動(dòng)脈壓波形變化參數(shù)分析（FloTrac）的術(shù)中液體治療對(duì)老年高危手術(shù)患者術(shù)后預(yù)后的影響。這是一項(xiàng)前瞻性、標(biāo)簽開放的隨機(jī)對(duì)照研究。將2013年10月至2014年11月138例≥65歲在北京大學(xué)第一醫(yī)院擬行腹部大手術(shù)的患者隨機(jī)分為兩組（每組69例）。對(duì)照組術(shù)中進(jìn)行常規(guī)監(jiān)測(cè)、按臨床現(xiàn)有常規(guī)進(jìn)行術(shù)中液體管理；目標(biāo)引導(dǎo)液體治療（GDT）組術(shù)中使用FloTrac/Vigileo系統(tǒng)監(jiān)測(cè)動(dòng)脈壓波形分析參數(shù)，通過(guò)輸液和血管活性藥的使用維持每博量變異度（SVV）＜13%、心臟指數(shù)（CI）≥2.5L/（min·m2）且平均動(dòng)脈壓（MAP）≥65mmHg。GDT組術(shù)后心血管并發(fā)癥發(fā)生率明顯少于對(duì)照組[2.9%（2/69）11.6%（8/69），＝0.049]；GDT組術(shù)后感染并發(fā)癥發(fā)生率略少于對(duì)照組，但差異無(wú)統(tǒng)計(jì)學(xué)意義[13.0%（9/69）26.1%（18/69），＝0.053]。術(shù)后總的并發(fā)癥發(fā)生率兩組間差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05）?；贔lotrac的GDT能減少高危老年患者術(shù)后心血管并發(fā)癥的發(fā)生，并有可能減少感染并發(fā)癥的發(fā)生，但對(duì)整體預(yù)后的影響尚需更大樣本量的研究證實(shí)。

液體治療；血流動(dòng)力學(xué)；監(jiān)測(cè)，術(shù)中；手術(shù)后并發(fā)癥；隨機(jī)對(duì)照試驗(yàn)

高?；颊咝g(shù)中如何做到恰當(dāng)補(bǔ)液一直是個(gè)令人困擾的問(wèn)題。補(bǔ)液過(guò)多易導(dǎo)致心肺負(fù)擔(dān)過(guò)重和組織水腫，增加術(shù)后并發(fā)癥甚至死亡風(fēng)險(xiǎn)[1]；而簡(jiǎn)單地限制液體輸注有可能影響組織灌注，給患者造成危害[2]。研究顯示目標(biāo)引導(dǎo)液體治療（goal-directed therapy，GDT）可以減少術(shù)后并發(fā)癥的發(fā)生[3?6]和死亡率[7]。對(duì)機(jī)械通氣期間動(dòng)脈壓波形變化參數(shù)分析（FloTrac）是GDT的監(jiān)測(cè)目標(biāo)之一，研究證實(shí)其監(jiān)測(cè)結(jié)果每搏量變異度（stroke volume variation，SVV）與容量反應(yīng)性有很好的相關(guān)性[8?10]。但目前有關(guān)FloTrac監(jiān)測(cè)參數(shù)SVV指導(dǎo)術(shù)中液體治療能否改善高?；颊哳A(yù)后的資料有限而且有爭(zhēng)議。Benes等[11]發(fā)現(xiàn)基于SVV監(jiān)測(cè)的容量?jī)?yōu)化措施能改善術(shù)中血流動(dòng)力學(xué)狀態(tài)、減少術(shù)后并發(fā)癥的發(fā)生；但另一項(xiàng)研究[12]并未發(fā)現(xiàn)SVV監(jiān)測(cè)的益處。本研究的目的是觀察基于機(jī)械通氣期間進(jìn)行FloTrac監(jiān)測(cè)的術(shù)中液體治療對(duì)老年高危手術(shù)患者預(yù)后的影響。

1 對(duì)象與方法

這是一項(xiàng)前瞻性、標(biāo)簽開放的隨機(jī)對(duì)照試驗(yàn)。研究方案得到北京大學(xué)第一醫(yī)院倫理委員會(huì)審核批準(zhǔn)（2013[662]），已在chictr.org注冊(cè)（ChiCTR-TRC-13003890）。所有受試者均簽署了知情同意書。本研究于2013年10月到2014年11月在北京大學(xué)第一醫(yī)院進(jìn)行。

1.1 研究對(duì)象及分組

入選標(biāo)準(zhǔn)為年齡≥65歲、美國(guó)麻醉醫(yī)師協(xié)會(huì)（American Society of Anesthesiologists，ASA）≥Ⅱ級(jí)、擬行擇期大手術(shù)（預(yù)計(jì)手術(shù)時(shí)間≥2h或失血量≥800ml）的患者。存在以下情況之一者排除：（1）術(shù)前有心律失常；（2）因先天性心臟病存在心內(nèi)分流；（3）因肺部疾病不能耐受8ml/kg潮氣量的機(jī)械通氣；（4）腎功能衰竭需要透析治療；（5）手術(shù)需開胸；（6）未取得知情同意。

由統(tǒng)計(jì)專業(yè)人員采用SAS9.2軟件按照區(qū)組隨機(jī)的方法生成隨機(jī)數(shù)字表，符合入選標(biāo)準(zhǔn)的患者，按照入組的先后順序根據(jù)隨機(jī)數(shù)字表的分組信息，按1∶1比例隨機(jī)分入對(duì)照組或GDT組。

1.2 麻醉和術(shù)中液體管理

術(shù)前常規(guī)禁食水和進(jìn)行腸道準(zhǔn)備。對(duì)照組術(shù)中監(jiān)測(cè)心電圖、有創(chuàng)動(dòng)脈壓、中心靜脈壓（central venous pressure，CVP）、脈搏氧飽和度、呼氣末二氧化碳、體溫和尿量；GDT組除上述常規(guī)項(xiàng)目外，還利用FloTrac（Adwards，美國(guó)）監(jiān)測(cè)SVV和心臟指數(shù)（cardiac index，CI）變化。所有患者均采用靜、吸復(fù)合麻醉，麻醉期間持續(xù)腦電雙頻指數(shù)（bispectral index，BIS）值40～60水平。氣管插管后行間歇正壓通氣，潮氣量8ml/kg，根據(jù)呼氣末二氧化碳調(diào)節(jié)呼吸頻率使動(dòng)脈血二氧化碳分壓維持在35～45mmHg（1mmHg＝0.133kPa）。

對(duì)照組按照現(xiàn)有臨床常規(guī)管理術(shù)中輸液，目標(biāo)是維持平均動(dòng)脈壓（mean arterial pressure，MAP）≥65mmHg、CVP 8～12mmHg（腹腔鏡手術(shù)氣腹建立穩(wěn)定后根據(jù)CVP波動(dòng)水平判斷）、尿量≥0.5ml/（kg·h）。醫(yī)師判斷容量足夠但MAP仍不能維持預(yù)計(jì)水平，則靜脈輸注去甲腎上腺素（noradrenaline）或多巴酚丁胺（dobutamine）維持血壓。

GDT組根據(jù)SVV和CI管理術(shù)中輸液：如SVV≥13%持續(xù)＞5min或?qū)η耙淮我后w治療出現(xiàn)陽(yáng)性反應(yīng)（表現(xiàn)為CI增加＞10%），則快速輸注乳酸林格液（lactated Ringer’s solution）250ml；5min后如SVV仍≥13%或者輸液后CI增加仍＞10%，則重復(fù)上述步驟。目標(biāo)是維持SVV＜13%、CI≥2.5L/（min·m2）且MAP≥65mmHg。如醫(yī)師判斷容量足夠但MAP和（或）CI仍不能維持預(yù)計(jì)水平，則輸注去甲腎上腺素維持血壓和（或）輸注多巴酚丁胺維持CI。

1.3 觀察終點(diǎn)

主要觀察終點(diǎn)是術(shù)后住院期間（截至術(shù)后30d）的并發(fā)癥發(fā)生率。急性腎損傷（acute kidney injury，AKI）的診斷依據(jù)對(duì)血肌酐（serum creatinine，SCr）和尿量的監(jiān)測(cè)，參照改善全球腎臟病預(yù)后組織（Kidney Disease：Improving Global Outcomes，KDIGO）診斷標(biāo)準(zhǔn)（2012年版）[13]做出；其他并發(fā)癥由1名臨床經(jīng)驗(yàn)豐富且對(duì)分組不知情的研究者進(jìn)行最終判斷，定義為術(shù)后30d內(nèi)新發(fā)的對(duì)患者有不良影響且需要醫(yī)療干預(yù)的情況。

1.4 統(tǒng)計(jì)學(xué)處理

采用SPSS14.0統(tǒng)計(jì)軟件進(jìn)行統(tǒng)計(jì)分析。計(jì)量資料用均數(shù)±標(biāo)準(zhǔn)差或中位數(shù)（Q1，Q3）表示，計(jì)數(shù)資料用例數(shù)（百分率）表示。計(jì)量資料兩組間比較采用檢驗(yàn)或Mann-Whitney檢驗(yàn)，計(jì)數(shù)資料組間比較采用2檢驗(yàn)。以術(shù)后發(fā)生并發(fā)癥為結(jié)局（其他情況為刪失）的變量進(jìn)行生存分析，采用Kaplan-Meier進(jìn)行描述，組間比較采用log-rank檢驗(yàn)。并采用Cox比例風(fēng)險(xiǎn)回歸模型校正基線有統(tǒng)計(jì)學(xué)差異的變量后對(duì)兩組間進(jìn)行比較。所有檢驗(yàn)均為雙側(cè)檢驗(yàn)，以＜0.05為差異有統(tǒng)計(jì)學(xué)意義。

2 結(jié) 果

2.1 患者入選及隨訪情況

共138例符合入選標(biāo)準(zhǔn)的患者進(jìn)入隨機(jī)分組，每組各69例，均完成了術(shù)中干預(yù)并隨訪至出院，其中GDT組有1例患者因家屬要求在術(shù)后第3天轉(zhuǎn)院治療。

2.2 兩組患者基線資料和圍術(shù)期情況比較

基線資料中，GDT組患者年齡高于對(duì)照組（＝0.049），其他指標(biāo)兩組間差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05；表1）。

表1 所有患者的基線資料

BMI: body mass index; NYHA: New York Heart Association; COPD: chronic obstructive pulmonary disease; ASA: American Society of Anesthesiologists; APACHE: Acute Physiology and Chronic Health Evaluation.*Alanine transaminase (ALT) and/or aspartate transaminase (AST) more than five times of the upper limit of normal.#Serum creatinine (SCr) ＞177μmol/L.△Smoking half a pack of cigarettes per day for at least 2 years

圍術(shù)期資料方面，GDT組麻醉時(shí)間和手術(shù)時(shí)間略短于對(duì)照組，但差異無(wú)統(tǒng)計(jì)學(xué)意義（分別為＝0.051和0.061）；GDT組術(shù)中多巴酚丁胺的使用比率明顯高于對(duì)照組（＝0.004），而麻黃堿的使用比率GDT組略低于對(duì)照組，但差異無(wú)統(tǒng)計(jì)學(xué)意義（＝0.087）。其他指標(biāo)兩組間差異無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05；表2）。

2.3 兩組患者術(shù)后情況比較

GDT組術(shù)后心血管并發(fā)癥發(fā)生率明顯低于對(duì)照組（＝0.049）；術(shù)后感染并發(fā)癥發(fā)生率GDT組略低于對(duì)照組，但差異無(wú)統(tǒng)計(jì)學(xué)意義（＝0.053）。其他術(shù)后并發(fā)癥發(fā)生率及總的并發(fā)癥發(fā)生率、并發(fā)癥初發(fā)時(shí)間兩組間差異均無(wú)統(tǒng)計(jì)學(xué)意義（＞0.05；表3）。建立Cox比例風(fēng)險(xiǎn)回歸模型校正年齡和手術(shù)時(shí)間后，術(shù)中動(dòng)脈波形衍生參數(shù)監(jiān)測(cè)并未顯著延遲術(shù)后并發(fā)癥初發(fā)時(shí)間（RR＝1.209，95% CI 0.679～2.153，＝0.518）。

表2 所有患者的術(shù)中資料

RBC: red blood cell; FFP: fresh frozen plasma.*Estimation of urine during surgery is impossible due to surgical practice, 8 and 3 patients in GDT group and control group respectively

3 討 論

本研究的結(jié)果顯示對(duì)于接受大手術(shù)的高危老年患者，術(shù)中根據(jù)機(jī)械通氣期間進(jìn)行FloTrac/Vigileo監(jiān)測(cè)的GDT可降低術(shù)后心血管并發(fā)癥發(fā)生率，并有減少術(shù)后感染并發(fā)癥的趨勢(shì)。

綜合現(xiàn)有文獻(xiàn)結(jié)果，術(shù)后各系統(tǒng)的并發(fā)癥發(fā)生率分別為心臟15.4%[6]、胃腸道15.9%[3]、AKI 8.3%[5]、感染25.5%[4]。本研究中對(duì)照組術(shù)后各系統(tǒng)并發(fā)癥發(fā)生率分別為心血管11.6%、胃腸道11.6%、AKI 8.7%、感染26.1%。說(shuō)明本研究所觀察患者的人群特征與以往研究基本一致。

Arulkumaran等[6]的薈萃分析發(fā)現(xiàn)GDT能減少高危手術(shù)患者術(shù)后心血管并發(fā)癥的發(fā)生，認(rèn)為這與在心輸出量監(jiān)測(cè)下、通過(guò)補(bǔ)液和正性肌力藥物改善組織氧輸送有關(guān)[14,15]。但在該薈萃分析所納入的22項(xiàng)研究中僅有2項(xiàng)研究采用了FloTrac監(jiān)測(cè)，且結(jié)果并不一致[11,16]。本研究顯示根據(jù)FloTrac監(jiān)測(cè)結(jié)果指導(dǎo)的術(shù)中液體管理減少了老年患者術(shù)后心血管并發(fā)癥的發(fā)生。本研究資料顯示GDT組和對(duì)照組的術(shù)中輸液量無(wú)明顯差異，但GDT組使用了更多的多巴酚丁胺，這可能是GDT組術(shù)后心血管并發(fā)癥發(fā)生率降低的主要原因。

表3 所有患者的主要觀察結(jié)果

Dalfino等[4]的薈萃分析發(fā)現(xiàn)GDT能減少術(shù)后感染并發(fā)癥的風(fēng)險(xiǎn)，認(rèn)為這與其改善患者的組織氧供有關(guān)[17]。但該薈萃分析所納入的26項(xiàng)研究中僅3項(xiàng)小規(guī)模研究采用了FloTrac監(jiān)測(cè)技術(shù)，結(jié)果也不一致[11,18,19]。本研究結(jié)果中雖然兩組患者間術(shù)后感染并發(fā)癥發(fā)生率的差異無(wú)統(tǒng)計(jì)學(xué)意義，但GDT組亦呈減少趨勢(shì)（＝0.053）。說(shuō)明根據(jù)FloTrac監(jiān)測(cè)指導(dǎo)術(shù)中容量管理可能降低術(shù)后感染風(fēng)險(xiǎn)，但仍需更進(jìn)一步的研究證實(shí)。

與以往的薈萃分析結(jié)果不同[3,5,20]，本研究并未發(fā)現(xiàn)GDT能減少術(shù)后胃腸道并發(fā)癥和AKI的發(fā)生，也未能減少總的術(shù)后并發(fā)癥發(fā)生率。但事實(shí)上在這些薈萃分析所納入的研究中僅有少數(shù)研究術(shù)中采用FloTrac監(jiān)測(cè)，而且這些研究均沒(méi)有發(fā)現(xiàn)FloTrac監(jiān)測(cè)組與對(duì)照組間有明顯差異。本研究結(jié)果中雖然術(shù)后總并發(fā)癥發(fā)生率兩組間差異無(wú)統(tǒng)計(jì)學(xué)意義，但GDT組確實(shí)低于對(duì)照組[30.4%（21/69）42.0%（29/69），＝0.157]?？紤]到本研究樣本量較小，術(shù)中以FloTrac動(dòng)脈壓波形分析參數(shù)為目標(biāo)的GDT對(duì)老年高?；颊哳A(yù)后的影響仍然值得進(jìn)一步研究。

4 結(jié) 論

基于機(jī)械通氣期間FloTrac監(jiān)測(cè)的術(shù)中GDT能降低高危老年患者術(shù)后心血管并發(fā)癥的風(fēng)險(xiǎn)，并有可能減少感染并發(fā)癥的發(fā)生，但對(duì)總體并發(fā)癥發(fā)生率的影響尚需更大樣本量的研究證實(shí)。

[1] Moller AM, Pederson T, Svendsen PE,. Perioperative risk factors in elective pneumonectomy: the impact of excess fluid balance[J]. Eur J Anaesthesiol, 2002, 19(1): 57?62.

[2] Holte, K, Foss NB, Andersen J,. Liberal or restrictive fluid administration in fast-track colonic surgery: a randomized, double-blind study[J]. Br J Anaesth, 2007, 99(4): 500?508.

[3] Giglio MT, Marucci M, Testini M,. Goal-directed haemodynamic therapy and gastrointestinal complications in major surgery: a meta-analysis of randomized controlled trials[J]. Br J Anaesth, 2009, 103(5): 637?646.

[4] Dalfino L, Giglio MT, Puntillo F,. Haemodynamic goal-directed therapy and postoperative infections: earlier is better. A systematic review and meta-analysis[J]. Crit Care, 2011, 15(3): R154.

[5] Brienza N, Giglio MT, Marucci M,. Does perioperative hemodynamic optimization protect renal function in surgical patients? A meta-analytic study[J]. Crit Care Med, 2009, 37(6): 2079?2090.

[6] Arulkumaran N, Corredor C, Hamilton MA,. Cardiac complications associated with goal-directed therapy in high-risk surgical patients: a meta-analysis[J]. Br J Anaesth, 2014, 112(4): 648?659.

[7] Aya HD, Cecconi M, Hamilton M,. Goal-directed therapy in cardiac surgery: a systematic review and meta-analysis[J]. Br J Anaesth, 2013, 110(4): 510?517.

[8] Hofer CK, Senn A, Weibel L,. Assessment of stroke volume variation for prediction of fluid responsiveness using the modified FloTrac and PiCCOplus system[J]. Crit Care, 2008, 12(3): R82.

[9] Button D, Weibel L, Reuthebuch O,. Clinical evaluation of the FloTrac/Vigileo system and two established continuous cardiac output monitoring devices in patients undergoing cardiac surgery[J]. Br J Anaesth, 2007, 99(3): 329?336.

[10] Mayer J, Boldt J, Wolf MW,. Cardiac output derived from arterial pressure waveform analysis in patients undergoing cardiac surgery: validity of a second generation device[J]. Anesth Analg, 2008, 106(3): 867?872.

[11] Benes J, Chytra I, Altmann P,. Intraoperative fluid optimization using stroke volume variation in high risk surgical patients: results of prospective randomized study[J]. Crit Care, 2010, 14(3): R118.

[12] Scheeren TW, Wiesenack C, Gerlach H,. Goal-directed intraoperative fluid therapy guided by stroke volume and its variation in high-risk surgical patients: a prospective randomized multicentre study[J]. J Clin Monit Comput, 2013, 27(3): 225?233.

[13] Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury[J].Off J Int Soc Nephrol, 2012, 2(Suppl 1): 1?138.

[14] Jhanji S, Vivian-Smith A, Lucena-Amaro S,. Haemodynamic optimisation improves tissue microvascular flow and oxygenation after major surgery: a randomised controlled trial[J]. Crit Care, 2010, 14(4): R151.

[15] Lobo SM, de Oliveira NE. Clinical review: what are the best hemodynamic targets for noncardiac surgical patients[J]? Crit Care, 2013, 17(2): 210.

[16] Cecconi M, Fasano N, Langiano N,. Goal-directed haemodynamic therapy during elective total hip arthroplasty under regional anaesthesia[J]. Crit care, 2011, 15(3): R132.

[17] Govinda R, Kasuya Y, Bala E,. Early postoperative subcutaneous tissue oxygen predicts surgical site infection[J]. Anesth Analg, 2010, 111(4): 946?952.

[18] Mayer J, Boldt J, Mengistu AM,. Goal-directed intraoperative therapy based on autocalibrated arterial pressure waveform analysis reduces hospital stay in high-risk surgical patients: a randomized, controlled trial[J]. Crit care, 2010, 14(1): R18.

[19] Van der Linden PJ, Dierick A, Wilmin S,. A randomized controlled trial comparing an intraoperative goal-directed strategy with routine clinical practice in patients undergoing peripheral arterial surgery[J]. Eur J Anaesthesiol, 2010, 27(9): 788?793.

[20] Cecconi M, Corredor C, Arulkumaran N,. Clinical review: goal-directed therapy—what is the evidence in surgical patients? The effect on different risk groups[J]. Crit Care, 2013, 17(2): 209.

（編輯: 周宇紅）

Effects of intraoperative goal-directed fluid therapy by using arterial wave analysis on outcome of high-risk elderly patients

XU Jing1, ZHANG Dan-Feng1, ZHU Sai-Nan2, WANG Dong-Xin1*

(1Department of Anesthesiology,2Division of Medical Statistics, Peking University First Hospital, Beijing 100034, China)

To investigate whether the intraoperative fluid therapy based on the parameters of arterial pressure wave analysis (FloTrac) could reduce the incidence of postoperative complications in the elderly patients after major surgery.This was a prospective, open-labeled, randomized controlled trial. One hundred thirty-eight patients at an age of ≥65 years who were scheduled for major abdominal surgeries in our department from October 2013 to November 2014 were randomized into 2 groups. In the control group, routine monitoring was performed and intraoperative fluid therapy was administered according to conventional practice. In the goal-directed therapy (GDT) group, hemodynamic monitoring was performed using the FloTrac/Vigileo system, and the intraoperative goals were to maintain stroke volume variation (SVV)＜13%, cardiac index (CI) ≥2.5 L/(min·m2), and mean arterial pressure (MAP) ≥65mmHg.The incidence of postoperative cardiovascular complications was significantly lower in the GDT group than in the control group[2.9%(2/69)11.6%(8/69),＝0.049]. The incidence of postoperative infectious complications was slightly lower in the GDT group than in the control group, but the difference was not statistically significant [13.0%(9/69)26.1%(18/69),＝0.053]. There was no significant difference between the 2 groups with regard to the overall incidence of postoperative complications.For the elderly patients undergoing major abdominal surgery, intraoperative GDT based on arterial pressure wave analysis decreases the incidence of postoperative cardiovascular complications, and also tends to decrease the incidence of postoperative infectious complications after surgery. However, its effects on the outcomes of the elderly need further study on larger samples.

fluid therapy; hemodynamics; monitoring, intraoperative; postoperative complications; randomized controlled trial

R614.2; R592

A

10.11915/j.issn.1671-5403.2015.04.067

2014?12?24;

2015?02?02

王東信, E-mail: wangdongxin@hotmail.com