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1.同濟大學(xué)附屬同濟醫(yī)院外科重癥監(jiān)護病房,上海 200065;2.同濟大學(xué)附屬同濟醫(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[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膿毒性休克患者死亡風(fēng)險的影響。

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日同濟大學(xué)附屬同濟醫(yī)院重癥監(jiān)護室收住的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或動脈二氧化碳分壓(PaCO2)<32 mmHg(1 mmHg=0.133 kpa);外周白細(xì)胞計數(shù)(WBC)>12×109/L或<4×109/L;符合以上2項。有感染證據(jù)或高度懷疑感染者。平均動脈壓(MAP)<65 mmHg或收縮壓下降>40 mmHg。排除標(biāo)準(zhǔn):住院時間<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),比較兩組補液量差異;同時按膿毒性休克后前2 d補液量分組,比較不同補液量組的生存率。

觀察指標(biāo)包括:性別、年齡、APACHE Ⅱ評分,感染性休克開始時SOFA評分、膿毒性休克2 d后SOFA評分、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)計軟件統(tǒng)計。正態(tài)分布計量資料采用均數(shù)±標(biāo)準(zhǔn)差,偏態(tài)分布計量資料采用中位數(shù)及四分位數(shù)范圍。用Kaplan-Maier進行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)險模型分析死亡風(fēng)險因素。

2 結(jié) 果

死亡組的APACHE Ⅱ評分及休克2 d后SOFA評分均高于存活組(P<0.05),見表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),其余各組生存率無差異,見圖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

對休克2 d后SOFA評與2 d累計液體平衡量最高組患者進行COX比例風(fēng)險回歸分析,結(jié)果顯示,休克2 d后高SOFA評分組(>5分)的死亡風(fēng)險是SOFA低評分組(<5分)的1.322倍(P<0.0001);2 d累計液體平衡量最高組的死亡風(fēng)險增高2.957倍(P=0.012),見表2。

3 討論

膿毒性休克患者的液體治療復(fù)雜,爭議頗多。本文對119例膿毒性休克患者不同液體治療與生存的關(guān)系進行了分析。結(jié)果顯示,死亡組休克發(fā)生后2 d補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],多個研究相繼證實對膿毒性休克病人行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)平衡限制性補液,因為這樣可減少機械通氣時間、院住時間[11]及提高生存率[12-13]。本文結(jié)果支持上述觀點。

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。說明病情重者對液體及血管活性藥的敏感性較差;為改善循環(huán),通常會給予反復(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補液反應(yīng)性良好者則少。本文結(jié)果也表明,患者的液體反應(yīng)性對預(yù)后有至關(guān)重要作用。近期指南推薦使用多種血流動力學(xué)指標(biāo)指導(dǎo)液體復(fù)蘇治療,同時強調(diào)對液體反應(yīng)性的評估[16]。臨床上,動態(tài)或靜態(tài)預(yù)測患者對液體反應(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;通過被動抬腿試驗[19]、超聲[20-21]、肺動脈導(dǎo)管、PiCCO等評價休克患者的補液反應(yīng)性有一定價值。但目前尚無單一標(biāo)可較好反應(yīng)膿毒性休克病人對液體的敏感性。

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

液體治療是通過補液方法改善機體血流動力學(xué)、維持重要器官血液灌注、糾正機體代謝障礙的措施。液體管理是以疾病治療指南為依據(jù),根據(jù)患者實際情況,規(guī)劃及時合理科學(xué)的液體治療個性化方案,使液體治療能最大限度地發(fā)揮作用。總之,膿毒癥患者液體反應(yīng)性對患者預(yù)后有影響;有效的液體管理對膿毒癥休克的治療起重要作用。但如何改善患者對液體的敏感性問題,仍需要進一步探索。

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