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1.同濟(jì)大學(xué)附屬同濟(jì)醫(yī)院外科重癥監(jiān)護(hù)病房,上海 200065;2.同濟(jì)大學(xué)附屬同濟(jì)醫(yī)院泌尿外科,上海 200065

膿毒性休克是由微生物及其毒素等直接或間接導(dǎo)致全身炎癥反應(yīng)綜合征(systemic inflammatory response syndrome,SIRS)并伴急性微循環(huán)障礙引起的組織灌注不足、循環(huán)血量減少、器官功能和細(xì)胞代謝紊亂的臨床綜合征。其年發(fā)病率0.3%,全世界年新發(fā)病例約1 800萬(wàn)[1]。如何提高膿毒性休克患者的預(yù)后已成為臨床醫(yī)師的一大難題。臨床工作中,補(bǔ)液是膿毒性休克治療部分措施,但至關(guān)重要。本文分析膿毒癥休克患者液體量與生存的關(guān)系以探討不同液體管理對(duì)膿毒性休克患者死亡風(fēng)險(xiǎn)的影響。

1 資料和方法

1.1 一般資料

收集2013年1月1日—2015年12月31日同濟(jì)大學(xué)附屬同濟(jì)醫(yī)院重癥監(jiān)護(hù)室收住的119例感染性休克患者。納入標(biāo)準(zhǔn):參照感染性休克診斷標(biāo)準(zhǔn)[2]:體溫>38 ℃或<36 ℃;心率>90次/min;呼吸頻率(f)>20次/min或動(dòng)脈二氧化碳分壓(PaCO2)<32 mmHg(1 mmHg=0.133 kpa);外周白細(xì)胞計(jì)數(shù)(WBC)>12×109/L或<4×109/L;符合以上2項(xiàng)。有感染證據(jù)或高度懷疑感染者。平均動(dòng)脈壓(MAP)<65 mmHg或收縮壓下降>40 mmHg。排除標(biāo)準(zhǔn):住院時(shí)間<1周;液體出入量資料記錄不全;年齡低于18歲;瀕死狀態(tài)。

1.2 方法

按患者28 d預(yù)后分為生存組(73例)與死亡組(46例),比較兩組補(bǔ)液量差異;同時(shí)按膿毒性休克后前2 d補(bǔ)液量分組,比較不同補(bǔ)液量組的生存率。

觀察指標(biāo)包括:性別、年齡、APACHE Ⅱ評(píng)分,感染性休克開(kāi)始時(shí)SOFA評(píng)分、膿毒性休克2 d后SOFA評(píng)分、每日出入量和住院天數(shù)。

1.3 數(shù)據(jù)處理

所有數(shù)據(jù)采用SPSS 19.0統(tǒng)計(jì)軟件統(tǒng)計(jì)。正態(tài)分布計(jì)量資料采用均數(shù)±標(biāo)準(zhǔn)差,偏態(tài)分布計(jì)量資料采用中位數(shù)及四分位數(shù)范圍。用Kaplan-Maier進(jìn)行2 d液體累積量四分位數(shù)分組患者的生存分析。用單因素分析、Cox比例風(fēng)險(xiǎn)模型分析死亡風(fēng)險(xiǎn)因素。

2 結(jié) 果

死亡組的APACHE Ⅱ評(píng)分及休克2 d后SOFA評(píng)分均高于存活組(P<0.05),見(jiàn)表1。

死亡組第1～2天每日液體量均大于生存組(P=0.031,<0.001)

7 d液體累積量亦明顯大于生存組(P<0.05),見(jiàn)圖1。

表1 生存組與死亡組患者基本資料比較Tab.1 Comparison of basic information of the survival group and the death group

圖1 生存組和死亡組1周內(nèi)每日液體量(右圖)和每日液體累積量(左圖)比較(P<0.05)Fig.1 Comparison of daily fluid balance and daily fluid cumulative balance of the survival group and the death group

在按2 d液體累積平衡量行四分位數(shù)分組患者中,液體累積量最高組病人生存率明顯低于液體累積量最低組患者(P=0.037),其余各組生存率無(wú)差異,見(jiàn)圖2。

圖2 不同2天液體累積量休克患者的生存分析Fig.2 Survival analysis of patients with septic shock stratified by quartiles of 2-day cumulative fluid balance

對(duì)休克2 d后SOFA評(píng)與2 d累計(jì)液體平衡量最高組患者進(jìn)行COX比例風(fēng)險(xiǎn)回歸分析,結(jié)果顯示,休克2 d后高SOFA評(píng)分組(>5分)的死亡風(fēng)險(xiǎn)是SOFA低評(píng)分組(<5分)的1.322倍(P<0.0001);2 d累計(jì)液體平衡量最高組的死亡風(fēng)險(xiǎn)增高2.957倍(P=0.012),見(jiàn)表2。

3 討論

膿毒性休克患者的液體治療復(fù)雜,爭(zhēng)議頗多。本文對(duì)119例膿毒性休克患者不同液體治療與生存的關(guān)系進(jìn)行了分析。結(jié)果顯示,死亡組休克發(fā)生后2 d補(bǔ)液量明顯大于生存組,提示休克早期液體復(fù)蘇是體內(nèi)液體累積的主要原因;2 d液體累積量最高四分位組膿毒性休克患者的生存率明顯低于液體累積量最低四分位組。后者與Sirvent等[3]研究結(jié)果一致。在Rivers提出早期目標(biāo)指導(dǎo)治療(early goal directed therapy,EGDT)后[4],多個(gè)研究相繼證實(shí)對(duì)膿毒性休克病人行EGDT并不改善預(yù)后[5-7];膿毒性休克后期液體正平衡反而增加患者死亡率[8-10]。大多學(xué)者主張,感染性休克后期在保證生命體征平穩(wěn)情況下,盡量予以液體負(fù)平衡限制性補(bǔ)液,因?yàn)檫@樣可減少機(jī)械通氣時(shí)間、院住時(shí)間[11]及提高生存率[12-13]。本文結(jié)果支持上述觀點(diǎn)。

本研究還表明,膿毒性休克生存組與死亡組7 d液體累積量存在差異,且以第2～3日最明顯。說(shuō)明病情重者對(duì)液體及血管活性藥的敏感性較差;為改善循環(huán),通常會(huì)給予反復(fù)的液體沖擊治療。研究表明,40%～72%危重癥患者液體反應(yīng)性良好[14-15],但在膿毒性休克患者中對(duì)補(bǔ)液反應(yīng)性良好者則少。本文結(jié)果也表明,患者的液體反應(yīng)性對(duì)預(yù)后有至關(guān)重要作用。近期指南推薦使用多種血流動(dòng)力學(xué)指標(biāo)指導(dǎo)液體復(fù)蘇治療,同時(shí)強(qiáng)調(diào)對(duì)液體反應(yīng)性的評(píng)估[16]。臨床上,動(dòng)態(tài)或靜態(tài)預(yù)測(cè)患者對(duì)液體反應(yīng)性的指標(biāo)包括收縮壓變異率、脈壓變異率[17-18]、每搏量變異率等;通過(guò)被動(dòng)抬腿試驗(yàn)[19]、超聲[20-21]、肺動(dòng)脈導(dǎo)管、PiCCO等評(píng)價(jià)休克患者的補(bǔ)液反應(yīng)性有一定價(jià)值。但目前尚無(wú)單一標(biāo)可較好反應(yīng)膿毒性休克病人對(duì)液體的敏感性。

表2 COX回歸分析Tab.2 Cox regression analysis

液體治療是通過(guò)補(bǔ)液方法改善機(jī)體血流動(dòng)力學(xué)、維持重要器官血液灌注、糾正機(jī)體代謝障礙的措施。液體管理是以疾病治療指南為依據(jù),根據(jù)患者實(shí)際情況,規(guī)劃及時(shí)合理科學(xué)的液體治療個(gè)性化方案,使液體治療能最大限度地發(fā)揮作用?？傊?膿毒癥患者液體反應(yīng)性對(duì)患者預(yù)后有影響;有效的液體管理對(duì)膿毒癥休克的治療起重要作用。但如何改善患者對(duì)液體的敏感性問(wèn)題,仍需要進(jìn)一步探索。

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