摘要:目的:探討Picco指導(dǎo)下的早期液體復(fù)蘇在膿毒性休克病人治療中的有效性。方法:回顧性分析了51例膿毒性休克病人,被隨機(jī)分為兩組:Picco組和對(duì)照組。Picco組22例病人接受Picco監(jiān)測(cè),以ITBVI及EVLW作為液體復(fù)蘇的指導(dǎo)指標(biāo),對(duì)照組29例病人在中心靜脈壓監(jiān)測(cè)下接受液體復(fù)蘇,然后記錄和比較2組病人在復(fù)蘇前及復(fù)蘇后的液體平衡量,乳酸及乳酸清除率,氧合指數(shù),同時(shí)比較兩組病人血管活性藥物的使用劑量,機(jī)械通氣時(shí)間,ICU住院時(shí)間及28天病死率。結(jié)果:1.在液體平衡方面,兩組在6h及48h液體正平衡量無(wú)明顯差異(6h:845±489ml vs 907±432 ml,P>0.05;24h:2004±1039ml vs1899±720ml,P>0.05),但24h Picco組液體平衡量明顯大于對(duì)照組(2204±1039VS 1899±720,P<0.05)。在復(fù)蘇后兩組病人血乳酸水平較復(fù)蘇前下降,而且在6h、24h、48h時(shí)間點(diǎn)的乳酸清除率Picco組均明顯高于對(duì)照組(6h:14.0±4.7%vs6.8±3.4%,P<0.05;24h:52.6±14.3%vs37.4±16.2%,P<0.05;48h:63.2±29.5%vs 55.9 ±32.4%,P<0.05);在復(fù)蘇后兩組病人氧合指數(shù)較復(fù)蘇前均有增加,在6h兩組之間無(wú)明顯差異(174.0 ±87.0VS 171.7 ±75.8 P>0.05);而在24h及48h Picco組比對(duì)照組明顯升高(24h:210.2±91.3 vs 182.5±85.8 P,<0.05;48h:296.4±101.3 vs 262.4±95.0,P <0.05)。2. Picco組與對(duì)照組比較,機(jī)械通氣通氣時(shí)間明顯減少(57.2(0–74)h vs72.4(0– 157)h,P=0.032),ICU住院時(shí)間縮短(6.5(3–14)d vs 8.3(4–21)d,p=0.014),而且Picco組的血管活性物質(zhì)使用劑量低于對(duì)照組(36.5±6.2mg vs 68.3±15.1mg,P= 0.001)。然而,兩組病人在28天病死率方面無(wú)明顯差異差異(40.91%vs37.94%,P=0.793)。結(jié)論:在膿毒性休克病人中運(yùn)用Picco系統(tǒng)能夠盡早改善組織灌注而不會(huì)加重容量負(fù)荷,同時(shí)減少血管活性物質(zhì)的劑量,提高患者的氧合功能,降低機(jī)械通氣時(shí)間和縮短ICU住院時(shí)間,然而不能降低28天病死率。
關(guān)鍵詞:Picco;膿毒性休克
The guiding role of Picco in the treatment of patients with septic shock
Hu Changzheng,Cao Ping,He Daizhong,Zeng Yong. Department Of Critical Care Medicine,Peple,s Hospital of BiShan District,ChongQing,402760.
Corresponding author:www.huchangzheng@163.com.
[Abstract]Objective:To investigate the effectiveness of early fluid resuscitation guided by Picco in the treatment of patients with septic shock.Methods:Fifty-one septic shock patients were retrospective analysed,which were divided into two groups randomly:Picco group and control group.twenty-two patients of Picco group received Picco monitoring,using ITBVIand EVLW as a indicator of fluid resuscitation,and twenty-nine patients of control group were received fluid resuscitation monitored by CVP .Then fluid balance quantity,lactate,lactate clearance rate,oxygenation index before and after resuscitation were recorded and compared,and the dosage of vasoactive drug,ventilation duration,the length of ICU,28-day mortality were also compared beween two groups.Results:1.In terms of fluid balance quantity,there was no significant difference at 6h and 48h after resuscitation between two groups(6h:845±489ml vs 907±432 ml,P>0.05;24h:2204±1039ml vs1899±720ml,P>0.05),but fluid balance quantity inPicco group was significantly greater than that in control group at 24h after resuscitation(2204±1039ml vs1899±720ml,P<0.05).The lactate of both groups after resuscitation were decreased than before,and the lactate clearance rate at 6h,24h,48h after resuscitation was significantly higher in Picco group than that in control group(6h:14.0±4.7%vs6.8±3.4%,P<0.05;24h:52.6±14.3%vs37.4±16.2%,P<0.05;48h:63.2±29.5%vs 55.9 ±32.4%,P<0.05).The oxygenation index of both groups after resuscitation were increased than before,there was no significant difference in oxygenation index at 6h after resuscitation between two groups(174.0 ±87.0VS 171.7 ±75.8,P>0.05),but oxygenation index in Picco group was significantly higher than that in control group at 24hand 48h after resuscitation(24h:210.2±91.3 vs 182.5±85.8,P<0.05;48h:296.4±101.3 vs 262.4±95.0,P<0.05).2.In comparation to control group,the ventilation duration of Picco group was significantly decreased(57.2(0–74)h vs72.4(0– 157)h,P=0.032),the length of ICU of Picco group was also shortened(6.5(3–14)d vs 8.3(4–21)d,p=0.014),and the dosage of vasoactive drug in Picco group was significantly lower(36.5±6.2mg vs 68.3±15.1mg,P= 0.001).However,there was no significant difference between two groups in terms of 28-day mortality(40.91%vs37.94%,P=0.793).Conclusion:The application of Picco system in the treatment of patients of septic shock is able to improve tissue perfusion as early as possible without increasing volume overload,and can improve the oxygenation function,decrease the dorsage of vasoactive drug,shorten the ventilation duration and the length of ICU.However,it can not reduce the 28-day mortality.
Key Words:Picco;Septic shock
嚴(yán)重膿毒癥及膿毒性休克是危重病人主要的死亡原因[1],病死率為14%-40%[2]。嚴(yán)重膿毒癥及膿毒性休克病人往往出現(xiàn)相對(duì)的或絕對(duì)的有效血容量不足,導(dǎo)致血流動(dòng)力學(xué)不穩(wěn)[3]。所以早期識(shí)別和處理血流動(dòng)力學(xué)和早期液體復(fù)蘇對(duì)于膿毒血癥的治療是關(guān)鍵的,而血流動(dòng)力學(xué)監(jiān)測(cè)在膿毒性休克的早期目標(biāo)導(dǎo)向的治療中發(fā)揮了重要的作用。最近幾十年見(jiàn)證了液體監(jiān)測(cè)技術(shù)快速的發(fā)展。Picco系統(tǒng)是一種包括了經(jīng)肺熱稀釋和連續(xù)性的脈搏示波分析的技術(shù)。它是一種微創(chuàng)技術(shù),可以提供對(duì)心輸出量的動(dòng)態(tài)監(jiān)測(cè),同時(shí)可以提供有關(guān)容量狀態(tài)和肺水方面的準(zhǔn)確信息,達(dá)到了連續(xù)監(jiān)測(cè)參數(shù)的目的,比如心輸出量(CO)、胸腔內(nèi)血容量(ITBV)、全心舒張末期容積指數(shù)(GEDVI)、血管外肺水含量(EVLW)、左心室收縮指(LVSI),外周血管阻力(SVR)和其他反映心功能和血管阻力變化的參數(shù)。在膿毒性休克病人的治療中Picco是一種有效的和先進(jìn)的血流動(dòng)力學(xué)監(jiān)測(cè)系統(tǒng)。先前的臨床研究探討了在膿毒性休克病人中運(yùn)用Picco來(lái)源的的生理參數(shù)(GEDVI、EVLW)與反映臨床的間接參數(shù)(CI、CVP、PaO2/FiO2)的邏輯關(guān)系,但是并沒(méi)有解決如何將這些參數(shù)整合到臨床中去以指導(dǎo)治療[4]。我們的研究目的是探討運(yùn)用Picco系統(tǒng)能否改善膿毒性休克病人的臨床結(jié)局以及反映病情的一些生理參數(shù)。
1.研究對(duì)象:
回顧性分析了2014年6月-2016年6月入住重慶市璧山區(qū)人民醫(yī)院重癥醫(yī)學(xué)科的51名膿毒性休克病人,將納入對(duì)象隨機(jī)分為兩組,其中Picco組(n =22)及對(duì)照組(n=29)。納入標(biāo)準(zhǔn):年齡≥18 歲;符合2014年嚴(yán)重膿毒癥或膿毒性休克的診斷標(biāo)準(zhǔn)[5]中膿毒性休克診斷標(biāo)準(zhǔn)的患者;急性呼吸窘迫綜合征(ARDS)的診斷標(biāo)準(zhǔn)采用柏林標(biāo)準(zhǔn)[6]。排除標(biāo)準(zhǔn):年齡小于18歲、排除心源性休克、肺栓塞、孕婦、家屬放棄治療。
2.研究方法:
2.1在Picco組,常規(guī)置入Picco導(dǎo)管,液體管理的目標(biāo)是維持最佳的有效循環(huán)容量,而且使用血管活性物質(zhì)來(lái)平均動(dòng)脈壓(MAP)不低于60mmHg,如果血容量達(dá)到最佳化(胸腔內(nèi)血容量指數(shù)ITBVI 達(dá)到 850-1000mL/m2),而血管外肺水含量超過(guò)10ml/kg,將使用利尿劑和腎臟替代治療策略來(lái)達(dá)到液體負(fù)平衡。如果心功能障礙導(dǎo)致患者循環(huán)衰竭(CI <2.5 L/ m2 /min),以2.5 rg/ kg /min 的開(kāi)始劑量使用多巴酚丁胺。
2.2在對(duì)照組,置入頸內(nèi)靜脈或者鎖骨下靜脈導(dǎo)管,通過(guò)使用中心靜脈壓(CVP)測(cè)定評(píng)估容量狀態(tài),目標(biāo)是維持CVP在8-12mmHg之間,如果CVP低于8mmHg,在超過(guò)30分鐘時(shí)間輸注500ml晶體液來(lái)維持CVP在8-12mmHg之間。如果目標(biāo)未達(dá)到,則重復(fù)劑量。如果CVP超過(guò)12mmHg,根據(jù)主治醫(yī)師的判斷使用呋塞米,硝酸甘油或者多巴酚丁胺。如果MAP低于60mmHg,以0.05rg /kg/ min 的劑量開(kāi)始使用去甲腎上腺素。如果MAP超過(guò)100mmHg,以0.5to3.0 rg /kg/ min的劑量使用硝酸甘油。
3.觀察指標(biāo):
包括兩組患者的一般資料,入院時(shí)的急性生理和慢性健康評(píng)分II(APACHEII),同時(shí)記錄患者復(fù)蘇前及復(fù)蘇后6h、24h、48h的液體正平衡量、乳酸清除率、氧合指數(shù);同時(shí)記錄患者使用血管活性藥物(去甲腎上腺素)的劑量、機(jī)械通氣時(shí)間、ICU住院時(shí)間、28天病死率。其中液體平衡量=液體入量-出量。乳酸清除率=初始乳酸值-各時(shí)間點(diǎn)乳酸值/初始乳酸值×%。
4.統(tǒng)計(jì)方法:采用SPSS19.0統(tǒng)計(jì)軟件,正態(tài)分布計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差表示,兩個(gè)獨(dú)立樣本比較采用t檢驗(yàn);非正態(tài)分布計(jì)量資料用中位數(shù)(范圍)表示,兩個(gè)獨(dú)立樣本比較采用秩和檢驗(yàn);計(jì)數(shù)資料比較采用卡方檢驗(yàn);P<0.05為差異具有統(tǒng)計(jì)學(xué)意義。
這項(xiàng)研究符合倫理學(xué)要求,得到了當(dāng)?shù)蒯t(yī)院倫理委員會(huì)的支持,同時(shí)征得患者及家屬的同意。
5.結(jié)果:
5.1.最終納入研究對(duì)象51例,對(duì)照組29例,Picco組22例。兩組入選對(duì)象的一般資料除了性別分布以外,包括年齡、感染部位、患者來(lái)源分類均無(wú)統(tǒng)計(jì)學(xué)意義(均P>0.05),說(shuō)明基線資料較均衡,有可比性。兩組病人在入院時(shí)APACHEII評(píng)分無(wú)明顯差異P>0.05),說(shuō)明治療前患者的疾病嚴(yán)重程度及可預(yù)測(cè)的病死率相當(dāng)。見(jiàn)表格1。
5.2.在液體平衡方面,兩組6h及48h液體正平衡量無(wú)明顯差異(P>0.05),而24h Picco組大于對(duì)照組(P <0.05);在復(fù)蘇后兩組病人血乳酸水平較復(fù)蘇前下降,而且在6h、24h、48h時(shí)間點(diǎn)的乳酸清除率Picco組均明顯高于對(duì)照組(均P<0.05);在復(fù)蘇后兩組病人氧合指數(shù)較復(fù)蘇前均有提高,在6h兩組之間無(wú)明顯差異(P>0.05);而在24h及48h Picco組比對(duì)照組明顯升高(P<0.05)。見(jiàn)表格2。
5.3. Picco組與對(duì)照組比較,機(jī)械通氣通氣時(shí)間縮短(P<0.05),ICU住院時(shí)間縮短(P<0.05),而且Picco組的血管活性物質(zhì)使用劑量低于對(duì)照組(P<0.05)。然而,兩組病人的28天病死率差異無(wú)統(tǒng)計(jì)學(xué)意義(P>0.05)。見(jiàn)表格3。
6.討論
由 Rivers[7]提出的早期目標(biāo)指導(dǎo)的液體復(fù)蘇(EGDT)強(qiáng)調(diào)迅速擴(kuò)容來(lái)增加心輸出量和氧輸送,從而恢復(fù)有效恢復(fù)血容量和減少組織和器官低灌注的時(shí)間。然而,過(guò)度的容量復(fù)蘇將會(huì)導(dǎo)致心衰以及隨后的肺水腫和低氧血癥的發(fā)生[8-9]。因此,識(shí)別恰當(dāng)?shù)娜萘繝顟B(tài)在膿毒性休克的治療中是很關(guān)鍵的。在臨床實(shí)踐中普遍使用CVP及肺動(dòng)脈契壓(PAWP),容易受到許多因素影響,包括心血管順應(yīng)性、胸腔內(nèi)壓力和機(jī)械通氣,因此不能準(zhǔn)確的反映心臟前負(fù)荷[10]。而Picco能夠充分反映血流動(dòng)力學(xué)參數(shù)以及心臟舒縮功能的變化,Picco在液體復(fù)蘇、液體管理、應(yīng)用利尿劑和評(píng)估治療方面具有重要作用[11]。與CVP相比,用ITBVI作為指標(biāo)對(duì)感染性休克患者進(jìn)行液體管理,3d的病情較1d改善,這種改善可能得益于對(duì)血容量的準(zhǔn)確判斷和適當(dāng)?shù)目焖傺a(bǔ)液速度[12]。先前的研究發(fā)現(xiàn)對(duì)膿毒性休克患者使用Picco監(jiān)測(cè)血流動(dòng)力學(xué),可以更全面地進(jìn)行血容量、全身血管阻力和心功能監(jiān)測(cè),科學(xué)指導(dǎo)患者液體復(fù)蘇、血管收縮藥物和正性肌力藥物的應(yīng)用[13-14]。在目前的研究的中,早期快速液體復(fù)蘇能夠有效降低血乳酸水平,而且Picco組較對(duì)照組提高6h、24h及48小時(shí)的血乳酸清除率(P<0.05),說(shuō)明Picco指導(dǎo)下的液體復(fù)蘇能夠更加迅速和有效地改善低血容量和減輕組織的低灌注狀態(tài)。而兩組患者的6h及48h的液體正平衡量的無(wú)差異性,這是因?yàn)镻icco的監(jiān)測(cè)能夠指導(dǎo)液體的選擇和利尿劑的應(yīng)用,從而減少過(guò)多的液體復(fù)蘇。已經(jīng)有大量的證據(jù)表明液體負(fù)平衡的有利影響,液體負(fù)平衡對(duì)于ARDS病人具有益處的觀點(diǎn)在臨床中已經(jīng)被廣泛接受和實(shí)踐[15]。所以對(duì)照組即使沒(méi)有Picco的監(jiān)測(cè),也會(huì)出現(xiàn)相似的液體平衡水平。
適當(dāng)?shù)耐庵苎茏枇捎脕?lái)維持組織灌注。膿毒性休克是一種典型的分布性休克,全身血管阻力的降低被認(rèn)為是膿毒性休克最早的血流動(dòng)力學(xué)改變。如果在6小時(shí)內(nèi)給予大量液體復(fù)蘇而不是使用血管活性物質(zhì),血流動(dòng)力學(xué)不會(huì)明顯改變,從而避免加劇組織器官缺血缺氧。只有在大量復(fù)蘇后血流動(dòng)力學(xué)仍然未改善的情況下才考慮使用血管活性物質(zhì)[14]。對(duì)于存在心功能損害的膿毒性休克患者,應(yīng)及早應(yīng)用正性肌力藥物,而不只是早期用血管收縮藥物提升平均動(dòng)脈壓[16]。目前的研究發(fā)現(xiàn)在Picco系統(tǒng)的監(jiān)測(cè)和指導(dǎo)下,與對(duì)照組相比,由于早期容量復(fù)蘇以及正性肌力藥物(多巴酚丁胺)的使用,血管活性藥物的使用劑量明顯減少(P<0.05)。因此,通過(guò)監(jiān)測(cè)全身性的血管阻力以及MAP的改變,Picco可以指導(dǎo)血管活性物質(zhì)的合理使用及維持正常范圍的外周血管阻力,這將使膿毒性休克患者受益。
在ARDS病人中,EVLW的增加是一個(gè)重要的病理變化,而且是引起ARDS病人生存率下降的主要原因。研究發(fā)現(xiàn)在具有高EVLW的ARDS病人中早期(48小時(shí)內(nèi))EVLW的變化與28天病死率相關(guān)[17],而且EVLW與肺損傷的嚴(yán)重程度成正相關(guān),而且與肺順應(yīng)性成負(fù)相關(guān)[18]。EVLW同樣與ARDS的嚴(yán)重程度,機(jī)械通氣天數(shù),ICU住院天數(shù),ARDS病死率相關(guān)[19]。研究發(fā)現(xiàn) PaO2/FiO2與EVLW以及液體平衡均成負(fù)相關(guān)[4,20],而EVLW影響氧合的機(jī)制尚不清楚[21]。另外有研究顯示限制性液體復(fù)蘇能夠?qū)е翧RDS模型小豬有更好的氧合功能[22]。在目前的研究中,與對(duì)照組相比,盡管24h液體平衡量Picco組大于對(duì)照組(P<0.05),但6h及48h液體總平衡量無(wú)差別,而Picco組氧合指數(shù)明顯高于同時(shí)間點(diǎn)的對(duì)照組(P<0.05),而且縮短了機(jī)械通氣時(shí)間(P<0.05),我們分析這是這得益于Picco對(duì)血容量和EVLW的動(dòng)態(tài)監(jiān)測(cè),當(dāng)ITBVI 達(dá)到 850-1000mL/m2,同時(shí)EVLW超過(guò)10ml/kg,表明容量負(fù)荷已經(jīng)達(dá)到最佳化,將會(huì)限制液體入量,同時(shí)利尿劑或者腎臟替代將會(huì)考慮使用。因此結(jié)果表明Picco指導(dǎo)下的液體復(fù)蘇能夠減輕膿毒性休克患者肺水,改善氧合功能,且不會(huì)增加容量負(fù)荷。
目前很少有隨對(duì)照試驗(yàn)來(lái)探索基于Picco來(lái)源的生理參數(shù)對(duì)于ARDS及膿毒性休克病人的治療效果[22]。由Zhang等人進(jìn)行的一項(xiàng)隨機(jī)對(duì)照試驗(yàn),比較了Picco來(lái)源的生理參數(shù)和CVP監(jiān)測(cè)下的治療,但由于Picco監(jiān)測(cè)下的治療的無(wú)效性,這項(xiàng)研究不得不提前終止,結(jié)果發(fā)現(xiàn)在Picco基礎(chǔ)上的膿毒性休克病人的治療并不能改善患者的臨床結(jié)局[15]。在我們的研究中,Picco組和對(duì)照組的28天病死率無(wú)明顯差異(P>0.05),這與先前的研究一致[15,22]。盡管Picco組的ICU住院時(shí)間縮短,但I(xiàn)CU住院時(shí)間并不是治療成功的可靠指標(biāo),因?yàn)镮CU的出院標(biāo)準(zhǔn)并不是一致的[23]。而最近的一項(xiàng)有關(guān)EGDT對(duì)于膿毒性休克病人臨床結(jié)局的meta分析發(fā)現(xiàn)EGDT能夠降低膿毒性休克病人ICU病死率,但不能降低患者的長(zhǎng)期病死率[23]。所以我們認(rèn)為Picco指導(dǎo)下的早期液體復(fù)蘇能夠減輕膿毒性休克患者早期病情,縮短ICU住院時(shí)間,但對(duì)患者長(zhǎng)期病死率的影響由于受到小樣本例數(shù)及回顧性研究的限制,目前尚缺乏強(qiáng)有力的證據(jù)。.
結(jié)論:膿毒性休克病人在Picco指導(dǎo)下的早期液體復(fù)蘇,能夠盡早改善組織灌注而不會(huì)加重容量負(fù)荷,同時(shí)減少血管活性物質(zhì)的使用劑量,提高患者的氧合功能,降低機(jī)械通氣時(shí)間和縮短ICU住院時(shí)間,然而不能降低28天病死率。在這方面需要大樣本的前瞻性隨機(jī)對(duì)照試驗(yàn)作進(jìn)一步的研究。
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