關(guān)注危重病人液體平衡(定稿)

1、關(guān)注危重病人液體平衡關(guān)注危重病人液體平衡徐穎鶴徐穎鶴目錄目錄 EGDT提高搶救成功率提高搶救成功率 液體超負(fù)荷增加危重病人死亡率液體超負(fù)荷增加危重病人死亡率 CVP監(jiān)測(cè)能準(zhǔn)確指導(dǎo)液體復(fù)蘇嗎？監(jiān)測(cè)能準(zhǔn)確指導(dǎo)液體復(fù)蘇嗎？ 白蛋白用于液體復(fù)蘇新觀點(diǎn)白蛋白用于液體復(fù)蘇新觀點(diǎn)Early Goal-Directed Therapy (EGDT): involves adjustments of cardiac preload, afterload, and contractility to balance O2 delivery with O2 demandChest 1992;101:1644Early

2、 Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic ShockRivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. NEJM 2001;345:1368.Study purpose: to evaluate the efficacy of early goal-directed therapy in patients present

3、ing to an emergency department with severe sepsis or septic shock (prior to ICU admission)Study design: prospective, randomized controlled, partially blinded, single center trialPatient randomized N=263Early goal directed therapy N=130Standard therapy N=133CVP 8-12 mm HgMAP 65 mm HgUrine Output 0.5

4、ml/kg/hrCVP 8-12 mm HgMAP 65 mm HgUrine Output 0.5 ml/kg/hrScvO2 70%SaO2 93%Hct 30%Antibiotics given at discretion of treating cliniciansAs soon as possible Mean 6.2hrsICU MDs blinded to study treatmentNEJM 2001;345:1368-77.At least 6 hoursof EGDTMean 8hrsTransfer to ICUCVP: central venous pressureM

5、AP: mean arterial pressureScvO2: central venous oxygen saturationEarly Goal-Directed TherapyNEJM 2001;345:1368-77.49.2%33.3%0102030405060Standard Therapy N=133EGDTN=130P = 0.01*Key difference was in sudden CV collapse, not MODSEarly Goal-Directed Therapy Results:28 Day MortalitySudden CV CollapseMOD

6、S21% vs 10% p=0.0222% vs 16% P=0.27NEJM 2001;345:1368-77.Mortality質(zhì)疑點(diǎn)質(zhì)疑點(diǎn)質(zhì)疑點(diǎn)CVP監(jiān)測(cè)能準(zhǔn)確指導(dǎo)液體監(jiān)測(cè)能準(zhǔn)確指導(dǎo)液體復(fù)蘇嗎？復(fù)蘇嗎？Objective: A systematic review of the literature to determine the following: (1)the relationship between CVP and blood volume, (2) the ability of CVP to predict fluid responsiveness, (3) the abili

7、ty of the change in CVP (CVP) to predict fluid responsiveness.The pooled correlation coefficient between theCVP and measured blood volume was 0.16 (95% CI,0.03 to 0.28; r= 0.02).1、The pooled correlation coefficient between baseline CVP and change in stroke index/cardiac index was 0.182、The pooled ar

8、ea under the ROCcurve was 0.56 3、The pooled correlation between CVP and change in stroke index/cardiac index was 0.11 4、The baseline CVP was 8.7 -2.3mm Hg in the responders, as compared to 9.7 - 2.2mm Hg in nonresponders (not signficant; p 0.3).結(jié)論結(jié)論 1、CVP與血容量之間相關(guān)性很低與血容量之間相關(guān)性很低 2、CVP或者或者CVP沒有能力判定補(bǔ)液對(duì)沒

9、有能力判定補(bǔ)液對(duì)血流動(dòng)力學(xué)的影響血流動(dòng)力學(xué)的影響 3、CVP不應(yīng)該用于醫(yī)生決策液體治療不應(yīng)該用于醫(yī)生決策液體治療Fluid Resuscitation in Septic shockA Positive Fluid Balance and Elevated Central Venous Pressure Are Associated With Increased Mortality 回歸性分析回歸性分析 The Vasopressin in Septic Shock Trial (VASST) study 778為感染性休克患者為感染性休克患者 研究目的是確定研究目的是確定CVP、液體平衡與死

10、亡、液體平衡與死亡率關(guān)系率關(guān)系Crit Care Med. 2011;39(2):259-65 12h液體平衡與CVP有關(guān)聯(lián)，24小時(shí)就沒有關(guān)聯(lián)CVP GroupNet Fluid Balancep SurvivorsNonsurvivorsAll Patients3444 (18615984) mL4429 (25376560) mL.001CVP 12 mm Hg3975 (23876614) mL5237 (31407773) mL.001Stop filling patients against central venous pressure, please!*Crit Care Me

11、d 2011 Vol. 39, No. 2Lees N, Hamilton M, Rhodes A: Clinical review:Goal-directed therapy in high risk surgicalpatients. Crit Care 2009; 13:231修正的修正的EGDTEGDT試驗(yàn)試驗(yàn)u1.鎮(zhèn)靜鎮(zhèn)痛u2.液體反應(yīng)性：CVP動(dòng)態(tài)變化；對(duì)于正壓通氣患者SVV/PPVu3.滴定MAP7585mmHgu4.P(cv-a)CO2u5.血管活性藥撤離試驗(yàn)血管活性藥血管活性藥物撤離試驗(yàn)物撤離試驗(yàn)液體超負(fù)荷，我們要重視液體超負(fù)荷，我們要重視的問題！的問題！Payen S, e

12、tal,for the Sepsis Occurrence in Acutely Ill Patients (SOAP)Investigators: A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care 12: R74, 2008液體積聚在為重病人中經(jīng)常發(fā)生Fluid Resuscitation in Septic shockA Positive Fluid Balance and Elevated Central Venous Pr

13、essure Are Associated With Increased Mortality 回歸性分析回歸性分析 The Vasopressin in Septic Shock Trial (VASST) study 778為感染性休克患者為感染性休克患者 研究目的是確定研究目的是確定CVP、液體平衡與死亡、液體平衡與死亡率關(guān)系率關(guān)系Crit Care Med. 2011;39(2):259-65 12h液體正平衡4.2 3.8 L 第四天液體正平衡11 8.9 L Quartile 1 (Dry)Quartile 2Quartile 3Quartile 4 (Wet)12 hrs Inta

14、ke, mL2900 (20503900)4520 (37005450)6110 (53307360)10,100 (843012,100) Output, mL2200 (11003920)1590 (9602560)1180 (6002070)1260 (6002400) Balance, mL710 (1321480)2880 (25103300)4900 (42905530)8150 (711010,100)Day 4 Intake, mL16,100 (12,80019700)18,500 (15,70022,500)22,800 (19,70026,700)30,600 (26,2

15、0036,000) Output, mL14,600 (11,50020100)11,000 (821014,500)9960 (694012,900)8350 (510012,300) Balance, mL1560 (7233210)8120 (62109090)13,000 (11,80014,700)20,500 (17,70024,500)1、2與4相比，死亡率下降3與4相比，有下降，但無(wú)統(tǒng)計(jì)學(xué)意義CVP GroupNet Fluid Balancep SurvivorsNonsurvivorsAll Patients3444 (18615984) mL4429 (25376560)

16、 mL.001CVP 12 mm Hg3975 (23876614) mL5237 (31407773) mL.001結(jié)論：液體超負(fù)荷增加死亡風(fēng)險(xiǎn)液體超負(fù)荷增加死亡風(fēng)險(xiǎn)Vincent JL,et al: Sepsis in European intensive care units: results of the SOAP study. Crit Care Med 2006; 34:344353.多因素回歸分析表明：入院多因素回歸分析表明：入院72小時(shí)液體平衡小時(shí)液體平衡時(shí)獨(dú)立的結(jié)果預(yù)測(cè)指標(biāo)：沒增加時(shí)獨(dú)立的結(jié)果預(yù)測(cè)指標(biāo)：沒增加1升的液體升的液體積聚，死亡風(fēng)險(xiǎn)增加積聚，死亡風(fēng)險(xiǎn)增加Fluid a

17、ccumulation survival and recovery of kidney function in critically ill patients with acute kidney injury.目的目的: If fluid accumulation is associated with mortality and non-recovery of kidney function in critically ill adults with acute kidney injury. 方法方法: Fluid overload was defined as more than a 10%

18、 increase in body weight relative to baseline, measured in 618 patients enrolled in a prospective multicenter observational study. Kidney Int 2009618 critically ill patients were examined the effect of fluid overload Figure 2. Mortality rate by final fluid accumulation relative to baseline weight an

19、d stratified by dialysis status. Reprinted from reference 20, with permission. a highly significant correlation was observed between mortality and the proportion of days in which fluid overload was present (P0.0001). 結(jié)論結(jié)論： In patients with acute kidney injury, fluid overload was independently associ

20、ated with mortality.The importance of fluid management inacute lung injury secondary to septic shock Chest 2009; 136: 102109Adequate initial fluid resuscitation 是6h內(nèi)給予大于20 ml/kg 液體和CVP大于 8 mm Hg. Conservative late fluid在7天內(nèi)有2天達(dá)到液體平衡或負(fù)平衡多因素回歸分析不能達(dá)到限制液體管理的是獨(dú)立的死亡危險(xiǎn)因素多因素回歸分析不能達(dá)到限制液體管理的是獨(dú)立的死亡危險(xiǎn)因素Wiedeman

21、n,-two fluid-management strategies, N Engl J Med ,2006PURPOSE: Optimal fluid management in patients with acute lung injury METHODS: compared a conservative and a liberal strategy of fluid management 結(jié)論結(jié)論: the conservative strategy of fluid management improved lung function and shortened the duration

22、 of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures.液體超負(fù)荷液體超負(fù)荷疾病嚴(yán)重、死亡疾病嚴(yán)重、死亡病理因素病理因素生物標(biāo)記生物標(biāo)記1、滲漏滲漏2、AKI3、心衰、心衰4、CVP誤導(dǎo)誤導(dǎo).1、心臟負(fù)荷增加、心臟負(fù)荷增加2、肺水則更多、肺水則更多3、機(jī)械通氣時(shí)間長(zhǎng)、機(jī)械通氣時(shí)間長(zhǎng)4、腎臟、腎臟靜水壓增加靜水壓增加-腎動(dòng)脈灌注少腎動(dòng)脈灌注少5、腹腔間隙綜合癥、腹腔間隙綜合癥影響腎功能影響腎功能Clin J Am Soc Nephrol 5: 733739, 2010

23、.對(duì)我們的提示對(duì)我們的提示 1、尿量少不是擴(kuò)容的絕對(duì)指證，擴(kuò)容有預(yù)防、尿量少不是擴(kuò)容的絕對(duì)指證，擴(kuò)容有預(yù)防AKI的作用，也可能帶來(lái)不好的結(jié)果。的作用，也可能帶來(lái)不好的結(jié)果。 2、補(bǔ)液不能改善腎功能和氧合，即要停止、補(bǔ)液不能改善腎功能和氧合，即要停止 3、對(duì)感染性休克在前、對(duì)感染性休克在前6小時(shí)積極液體復(fù)蘇有益，小時(shí)積極液體復(fù)蘇有益，當(dāng)病情進(jìn)展，需要控制液體輸入，當(dāng)病情進(jìn)展，需要控制液體輸入， 4、可在利尿劑有效前提下使用利尿劑，利尿、可在利尿劑有效前提下使用利尿劑，利尿劑無(wú)效，要及時(shí)改為劑無(wú)效，要及時(shí)改為CRRT白蛋白，老話題，新進(jìn)展？維持血漿膠體滲透壓（）。的由白蛋白完成，并在循環(huán)血液與細(xì)胞

24、外液之間動(dòng)態(tài)交換，維持血液與細(xì)胞外液的膠體滲透壓的平衡。物質(zhì)轉(zhuǎn)運(yùn)作用。是脂類、激素、酶、電解質(zhì)、維生素、藥物等許多物質(zhì)轉(zhuǎn)運(yùn)的最重要的載體。是體內(nèi)重要的自由基清除劑。但是，這一功能在危重病的意義尚不清楚 。其他功用。調(diào)節(jié)細(xì)胞凋亡、抗凝、維持酸堿平衡等。白蛋白的生理作用白蛋白的生理作用 的。 白蛋白靜脈輸注后分鐘內(nèi)可將.倍體積的水分吸入血循環(huán)。 是人體細(xì)胞外液中含量最多的蛋白質(zhì)，具有親水性，可以自由通過毛細(xì)血管壁。 正常更新穩(wěn)定，每天大約。 半衰期天，平均天。白蛋白的生理作用及特白蛋白的生理作用及特點(diǎn)點(diǎn) 低蛋白血癥低蛋白血癥增加危重病增加危重病人死亡率嗎？人死亡率嗎？血漿白蛋白含量不僅僅是患者的營(yíng)

25、養(yǎng)指標(biāo)，更重要的是危重血漿白蛋白含量不僅僅是患者的營(yíng)養(yǎng)指標(biāo)，更重要的是危重患者并發(fā)癥和病死率的重要預(yù)測(cè)指標(biāo)患者并發(fā)癥和病死率的重要預(yù)測(cè)指標(biāo) Mangialardi等總結(jié)了北美7個(gè)ICU的臨床資料，表明低白蛋白血癥與ARDS的發(fā)生率和病死率顯著相關(guān)。 根據(jù)一項(xiàng)隊(duì)列研究所做的分析，危重病患者血清白蛋白濃度每下降2.5 g/L，可增加24%26%的死亡危險(xiǎn)，調(diào)整了危險(xiǎn)因素和基礎(chǔ)疾病以后,這種危險(xiǎn)依然存在。 從Medline、Cochrane Library和EMBASE等數(shù)據(jù)庫(kù)收集到的71份組群研究提示：血清白蛋白濃度與患者的預(yù)后和病情嚴(yán)重程度密切相關(guān)。白蛋白低于25 g/L的危重患者并發(fā)癥發(fā)生率將

26、提高4倍，病死率升高6倍。絕大部分危重患者死亡前的血漿白蛋白都難糾正到正常水平。 是否需要補(bǔ)充白蛋白？ 缺什么補(bǔ)什么，天經(jīng)地義！缺什么補(bǔ)什么，缺什么補(bǔ)什么，真的是天經(jīng)地真的是天經(jīng)地義嗎？義嗎？令人失望的結(jié)果 Foley等：給予白蛋白，并使其血白蛋白g/L，與不給予白蛋白的對(duì)照，病死率、住院日、住時(shí)間、機(jī)械通氣時(shí)間均無(wú)差異。 Golub和Rubin的研究結(jié)果與之相似。 Foley E F,BorlaseB C,DzikW H,et al.Albumin supplementation in the criticallyill: a prospective, randomized trialJ.A

27、rch Surg,1990,125:739 742 Golub R, Sorrento J J, Cantu R, et al.Efficacy of albumin supplementation inthe surgical intensive care unit: aprospective, randomized studyJ.CritCareMed,1994,22:613 619. Rubin H, Carlson S, DeMeo M, et al.Randomized, doubled2blindstudy ofintervenous human albumin in hypoal

28、bu2minemicpatients receiving totalparenteralnutritionJ.Crit CareMed,1997,25:249252.危重病患者接受人體白蛋白危重病患者接受人體白蛋白: :隨機(jī)對(duì)照研究的系統(tǒng)評(píng)價(jià)隨機(jī)對(duì)照研究的系統(tǒng)評(píng)價(jià)Cochrane協(xié)作網(wǎng)創(chuàng)傷協(xié)作組完成系統(tǒng)評(píng)價(jià)一共納入了32項(xiàng)隨機(jī)對(duì)照試驗(yàn)(RCT) 使用白蛋白組與對(duì)照組相比,死亡相對(duì)危險(xiǎn)升高約1.68倍,死亡率增加約6% 燒傷患者中,死亡危險(xiǎn)更趨明顯(RR=2.40) 在低蛋白血癥患者亞組, 雖然差異沒有統(tǒng)計(jì)學(xué)意義,但接受白蛋白治療的患者中,死亡率仍呈現(xiàn)上升趨勢(shì) 軒然大波軒然大波的文章的文章199

29、8年英國(guó)醫(yī)學(xué)雜志 （BMJ1998； 317:235-240 ） 結(jié)論：沒有證據(jù)證明給予白蛋白可降低包括低血容量、燒傷或低白蛋白血癥等危重病人的死亡率。相反,強(qiáng)烈提示其可增高死亡率 輸注白蛋白不能改善患者預(yù)后的可能原因 適應(yīng)性反應(yīng)。適應(yīng)性反應(yīng)。 蛋白質(zhì)結(jié)合的重要性受到了質(zhì)疑。蛋白質(zhì)結(jié)合的重要性受到了質(zhì)疑。 血管內(nèi)皮通道開放，白蛋白滲漏到組織間隙中，血管血管內(nèi)皮通道開放，白蛋白滲漏到組織間隙中，血管外的白蛋白還可以進(jìn)入到不能發(fā)生交換的部位，如腸外的白蛋白還可以進(jìn)入到不能發(fā)生交換的部位，如腸壁以及手術(shù)或創(chuàng)傷的傷口。壁以及手術(shù)或創(chuàng)傷的傷口。 白蛋白結(jié)構(gòu)的改變。白蛋白結(jié)構(gòu)的改變。 白蛋白可以通過主動(dòng)運(yùn)

30、輸進(jìn)入細(xì)胞內(nèi)。白蛋白可以通過主動(dòng)運(yùn)輸進(jìn)入細(xì)胞內(nèi)。 白蛋白及其替代品對(duì)血液的影響白蛋白及其替代品對(duì)血液的影響 。2001年, Wikes等另一個(gè)基于RCT的系統(tǒng)評(píng)價(jià)在Ann Intern Med上發(fā)表 415個(gè)相關(guān)研究中納入了55項(xiàng)符合標(biāo)準(zhǔn)的RCT 白蛋白治療組與對(duì)照組相比,其死亡率相對(duì)危險(xiǎn)(RR)為1.11,意味著白蛋白治療并不增加死亡風(fēng)險(xiǎn)外科手術(shù)或創(chuàng)傷、低蛋白血癥、腹水等)進(jìn)行的亞組分析,結(jié)果也都未證明白蛋白治療與死亡風(fēng)險(xiǎn)相關(guān) 系統(tǒng)評(píng)價(jià)的價(jià)值就正在于揭示問題和為下一步的研究提出方向 The SAFE study investigators. A comparison of albumin a

31、nd saline for fluid resuscitation in the intensive care unit在澳大利亞和新西蘭在澳大利亞和新西蘭完成的前瞻性、多中完成的前瞻性、多中心、隨機(jī)、雙盲試驗(yàn)心、隨機(jī)、雙盲試驗(yàn)包括包括16個(gè)個(gè)ICU 的的6 997例患者。例患者。3 500例患者接受生理例患者接受生理鹽水治療鹽水治療,3 497例患者例患者接受接受4%白蛋白治療白蛋白治療NEnglJMed,2004,350:2247 2256白蛋白和生理鹽水在容量復(fù)蘇中的比較研究白蛋白和生理鹽水在容量復(fù)蘇中的比較研究結(jié)論：在結(jié)論：在ICU中，用中，用4%白蛋白和生理白蛋白和生理鹽水做液體復(fù)蘇

32、結(jié)果是一樣的鹽水做液體復(fù)蘇結(jié)果是一樣的Sepsis occurrence in acutely ill patients: Isalbumin administration in the acutely ill associated with increased mortality?results of the SOAP study 歐洲危重病協(xié)會(huì)開展了多國(guó)歐洲危重病協(xié)會(huì)開展了多國(guó)多中心研究多中心研究 危重病患者進(jìn)行危重病患者進(jìn)行60 d隨訪觀隨訪觀察察,以在以在 ICU 中是否接受白中是否接受白蛋白治療分為兩組。蛋白治療分為兩組。 3 147例患者中例患者中,354例例(11.12%)接受了

33、白蛋白治療接受了白蛋白治療, 2 793例例(88.18%)沒有接受沒有接受白蛋白治療白蛋白治療 經(jīng)過經(jīng)過COX 風(fēng)險(xiǎn)模型校正風(fēng)險(xiǎn)模型校正 339個(gè)評(píng)分接近的配對(duì)研究個(gè)評(píng)分接近的配對(duì)研究.Crit Care,2005,9:R745- 754結(jié)論卻令人沮喪結(jié)論卻令人沮喪:危重患者使用白蛋危重患者使用白蛋白確實(shí)會(huì)造成生存白確實(shí)會(huì)造成生存率下降率下降A(chǔ)lbumin (n = 339)No albumin (n = 339)p valueAge, mean SD62.6 15.162.6 17.10.365Male gender (%)221 (62.2)206 (60.8)0.693Chronic

34、diseases (%)COPD37 (10.9)33 (9.7)0.614Cancer61 (18.0)62 (18.3)0.921Heart failure40 (11.8)43 (12.7)0.725Diabetes27 (8.0)34 (10.0)0.347Liver cirrhosis30 (8.8)26 (7.7)0.577Hematologic cancer12 (3.5)10 (2.9)0.665HIV/AIDS5 (1.5)7 (2.1)1.000Surgical admissions (%)208 (61.4)215 (63.4)0.579SAPS II score, mean SD41.7 17.241.6 18.10.664SOFA score, mean SDa7.1 4.16.7 4.40.126Organ failureaRespiratory106 (31.3)100 (29.5)0.616Hepatic16 (4.7)15 (4.4