脓毒症的液体治疗课件

1、脓毒症的液体治疗 VISEP试验解读EpidemiologyManagement : guidelinesInitial resuscitationDiagnosisAntibiotic therapySource controlFluid therapyVasopressorsInotropic therapySteroidsRh APCBlood product administrationk.Mechanical ventilationl. Sedation m. Glucose controln. Renal replacemento. Bicarbonate therapyp. De

2、ep vein thrombosis prophylaxisq. Stress ulcer prophylaxisDellinger R Int Care Med 2004;30:536-555 6 HRandomizationEGDTEarly Goal Directed Therapy : ResultsEGDT : mortality 16% at 28 d12% at 60 dRivers E N Engl J Med 2001;345:1368-77Dellinger, et. al. Crit Care Med 2004, 32: 858-873.colloidsWhole blo

3、odPRBCFFPPlasma proteinsblood/blood productsnatural colloidsAlbumin 0.9% NaCIRingers lactatcrystalloidsGelatinDextran HESsyntheticcolloidsVolume replacementShould we transfuse Red Blood Cells?A comparison of albumin and saline for fluid resuscitation in the ICUProbability of Survival0,5028AlbuminN-S

4、aline1,0 Finfer S et al. N Engl J Med 2004;350:2247-56RCT stydy6997 PatientsControl group: N-Saline Study group: 4% AlbuminMulticenter trial Albumin vs. CrystalloidsSAFE Study Australia/New Zealand6997 patients: 3497 albumin, 3500 normal salineMortality: 726 p. albumin, 729 p. normal salineSingle or

5、gan failure no difference ICU days: 6.5 d albumin, 6.2 d normal salineVent. days: 4.5 d albumin, 4.3 d normal salineRenal replacement: 0.5 d albumin, 0.4 d salineOutcome: 28 d mortality similarAUS/NZ Int.Care Soc.Clin.Trial Group NEJM 2004;350:2247-56SAFE study任何死亡原因的相对风险度0.5 1.0 2.0AlbuminBetterSal

6、ineBetter0.99 (0.91-1,09)1.36 (0.99-1.86)0.96 (0.88-1.06)0.87 (0.74-1.02)1.05 (0.94-1.17)0.93 (0.61-1.41)1.00 (0.91-1.09)总数726/3473729/3460创伤 是81/59659/590 否641/2831666/2830重度脓毒血症 是185/603217/615 否518/2734492/2720ARDS 是24/6128/66 否697/3365697/3354适应症 白蛋白 生理盐水 风险比值 (CI) 死亡例数/总例数N Engl J Med 2004;350:

7、2247Preferred plasma volume expanders for critically ill patients: results of an international surveySchortgen F et al. Intensive Care Med 2004; 30: 2222-29CRYCO Study group515 ICUs 75 item questionairevolume replacementhemodynamicstabilizationfluid-homeostasiscoagulationsideeffectsSchortgen F. et a

8、l. Lancet 2001;357:911-916Schorgen study没有肾功能衰竭的群体DaysN=64N=65P=0.018Observation periods of HES studies w/o renal impairment1 dayLondon et al. (J Cardiothoracic Anesth 1989)14 daysDeman et al. (Nephrol Dial Transplant 1999)6 hoursVogt et al. (Anesth Analg 1996)5 daysBoldt et al. (Intense Care Med 19

9、98)1 dayAllison et al. (J Trauma 1999)3 daysKumle et al. (Anesth Analg 1999)perioperative - 1 dayBoldt et al (J Cardiothoracic Anesth 2000)perioperative Dehne et al. (J Clin Anesth 2001)3 days (blood); 4 days (urine)Jungheinrich et al. (Anesth Analg 2002)2 daysBoldt et al. (Intens Care Med 2003)8 da

10、ys; FU 3 days after infusion Neff et al. (Anesth Analg 2003)Observation periodAuthorVISEP studyG. Marx, MDDept. of Anaesthesiology and Intensive Care Medicine,Friedrich-Schiller-University, Jena,Germany (德国耶拿大学)30个中心随机对照临床试验最新的评价HES治疗重度脓毒血症和感染性休克病人的多中心试验！Hemohes 10% Fa. B. Braun (HES 200 / 0.5)羟乙基淀粉

11、平均分子量 200 000分子取代级 0.45-0.55C2/C6 比值 6:1生产商推荐的每日最大用量 20 ml / kg BW/日 2.0 g / kg (75kg的病人 1,500 ml/日)扩容效能 130-150%扩容效果: 中等 (3-4 hours)容量治疗用药 Dieterich H-J.: J Trauma 2003起病24小时之内的重度脓毒血症和感染性休克（发病12小时之内的ICU获得性重度脓毒血症/感染性休克）。纳入标准年龄 1000 ml HES 严重的急慢性肾功能障碍 (既往已知的肌酐水平 320 mol/L 或需要透析治疗)颅内出血随机化分组时FiO2 0,7严重

12、头部创伤伴水肿心功能衰竭 (NYHA IV)应用免疫抑制剂DNR-order预计生存期 28 days排除标准 CVP 12 mmHg平均动脉压 70 mmHg中心静脉 氧饱和度 70% 测定点 :第1天: 1, 2, 4, 6, 8, 12 h第2-4天: Q 12 h第4天: Q 24 h 血流动力学目标24h12h随机化入选病例晶体容量替代治疗 (Sterofundin)胶体容量替代治疗直至用量上限(20 mL/kgBW) (HES)21天ICU前在ICU研究流程 31.78336.4100 病房医源性22.15823.364ICU医源性44.311639.3108社区获得性感染源%n%

13、nHESn = 262Ringerslactaten = 27555.014.456.853.012.954.4SAPS 20.06.720.619.06.520.3APACHE 67.013.364.468.014.164.9年龄MedianSDMeanMedianSDMean HESn = 262Ringers lactaten = 275VISEP 研究基础值3.8104.412心脏超声 (TTE or TEE)24.16324.467PICCO5.0136.618PA导管血流动力学监测24.16326.568ScvO2 70%31.38231.180MAP 70 mm HG21.055

14、19.851CVP 8 mm Hg5.31410.930无需透析的慢性肾衰6.51711.632心衰 NYHA II-III30.58030.283糖尿病60.315859.6164性别 (男)%n%nHESn = 262Ringerslactaten = 275VISEP 研究- 基础值 II -414.538414.640FFP nos.226.068221.559RBC nos.80014.137100011.331 明胶50016.44350011.632 HES 10 %50034.49050034.294 HES 6%200069.5182200074.6205 晶体容量负荷(随机

15、分组前12小时内)Medianml%nMedian ml%nHESn = 262Ringerslactaten = 275VISEP Trial (HES vs. 乳酸林格氏液) - 基础资料 III -20,02413,000max40,56833,507max2,4001463,7875000-24 hours3,4001005,9605000-48 hours晶体medianminmedianminHESn = 262晶体n = 275VISEP Trial (HES vs. 乳酸林格氏液) - 晶体容量替代治疗 (ml) -3,170 ml HES16,905 ml non-HES f

16、luids=15.3 Ratio of HES to non-HES fluids in the HES group (day 0-4) 平均动脉压中心静脉压中心静脉血氧饱和度10075500% of 达到综合目标的病人数25100200300400hours500600乳酸林格氏液 n=150HES n=146p=0.024血流动力学目标 (CVP, MAP, ScvO2) 24.1%26.7%0%25%50%75%28-day 死亡率死亡率 (%)n=274n=262乳酸林格氏液HESp=0.48n=274n=26133.9%41.0%0%25%50%75%90-day 死亡率p=0.11

17、死亡率Ringers lactate n=274p=0.141007550250存活率 %HES n=261020406080100days 存活率对肾脏的影响75.009.1874.1874.00 8.7173.44ScvO2 (%)75.5013.6376.2975.0013.9477.16MAP (mm Hg)12.005.3012.1012.005.1311.48CVP (mm Hg)126.8077.90141.99120.0085.72145.90血清肌酐 (mol/L)MedianSDMeanMedianSDMeanHESn = 262Ringers lactaten = 275

18、VISEP Trial (HES vs. 乳酸林格氏液) - 干预开始 -尿量 DiuresisRingers LactateHESDays 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21500045004000350030002500200015001000 500 0ml肌酐平均 SOFA 评分7.53MeanRingers lactaten = 2743.62SD6.75Median8.0MeanHESn = 2624.05SD7.29Median0.8p0.501.001.301.341.001.191.23CNS肝脏肾脏

19、凝血呼吸心血管SOFA-亚评分0.520.840.552.481.90MeanRingers lactate 0.801.050.820.581.10SD0.110.420.112.571.76Median0.521.120.752.441.83MeanHES0.781.260.860.601.17SD0.090.670.462.501.80Median1.00.020.00010.580.51p 并发症发病率0.001 22 ml/kg/BWHES 22 ml/kg/BW57.6%30.9%0%25%50%75%22.8%33.0%0%25%50%75%28-day 死亡率90-day 死亡

20、率死亡率 (%)n=162n=100HES 22 ml/kg BW/day *n=162n=99p=0.071P0.0001* on at least one study day HES 22 ml/kg BW/天亚组死亡率 从28天到90天之间死亡率的进展+ 27%+ 15.3%0%10%20%30%绝对死亡率的增加 (%)*on at least one study day+ 9.8%+ 9.2%HES 22 ml/kg BW/day* HES ITTCrystalloid+ 6.8% PROWESS Trial APC PROWESS Trial placebo1007550250存活率

21、 %020406080100daysHES 22 ml/kg BW/day n=162HES 22 ml/kg BW/day * n=99* on at least one study dayP 0.0001 存活率 HES 22 ml/kg/BW 0.003812.710.556.57.2 RBC nos0.00059.57.89.8177.713.2 不用血管活性和 正性心肌药物天数0.011167.813.3197.315.7 不用正性心肌药物天数0.003157.712.0187.714.5 不用血管活性药物天数 0.28003.21.802.81.49 不用抗生素天数0.000540

22、36.349.09135.966.5 无需肾脏替代治疗的天数22 ml/kg BW/day * n = 100HES 22 ml/kg BW/dayn = 162* on at least one study dayHES 22 ml/kg/BW 33.6%30.9%0%25%50%75%24.2%22.8%0%25%50%75%28-day 死亡率90-day 死亡率死亡率 (%)n=256n=162HESRingers lactaten=256n=162p=0.747p=0.562HES 22 ml/kg/BW vs 乳酸林格氏液 0.6150.901.221.181.001.221.24

23、 CNS0.9970.050.850.550.100.800.51 肝脏0.2260.501.191.000.421.040.84 肾脏0.2230.160.910.660.100.830.54 凝血0.3212.500.602.422.570.582.49 呼吸0.0111.431.151.61.751.111.89 心血管SOFA-亚组评分0.5564.73.325.815.002.945.62SOFApMedianSDmeanMedianSDmeanHES 22 ml/kg BW/dayn = 162晶体液n = 257 晶体液 vs. HES 22 ml/kg BW/天 14.8197

24、22928.23167258肾脏替代治疗的天数1.0003.716263.52579不良反应出血0.95666.716210866.9257172输RBC的病人数安全性急性肾衰肾脏替代治疗肾衰5644n乳酸林格氏液254254N22.117.3%5042nHES 22 ml/kg/BWn = 162162162N30.925.9%0.0440.035p 乳酸林格氏液 vs. HES 22 ml/kg BW/天 0.14256.57.247.06.4 RBC nos.0.483177.713.2167.912.7 Days w/o vasopressor and inotropic suppor

25、t0.481197.315.7197.815.0 Days w/o inotropic support0.442187.714.5187.614.2 Days w/o vasopressor support0.70502.81.4902.881.59 Days w/o antibiotics0.7639135.966.59135.865.9 Days w/o renal replacement therapy0.6537837.356.47636.956.4 Ventilator-free days0.6751216.918.61317.319.1 ICU LOS daysSecondary

26、endpointspMedianSDmeanMedianSDmeanHES w/o PVn = 162Crystalloid w/o PVn = 257Subgroup morbidity crystalloid vs. HES 22 ml/kg BW/day 应用 HES 10% (200/0.5)实施容量治疗可以更加迅速达到血流动力学状态的稳定。HES组发生急性肾衰和需要肾脏替代治疗的频率更频繁。两组在28天死亡率方面没有显著性差异。HES组90天的死亡率有增加的趋势 (33.9% vs 41.0%) (p=0.11) 。 总结 I（单变量分析 ）HES累积用量的增加与90天死亡率的增加有关联 (p=0.0015)。 HES累积用量增加，而非乳酸林格氏液，可能导致肾衰和需求肾脏替代治疗，并且与基础的肌酐清除率无关。总结 II（多变量分析 ）HES 10% (200/0.5) 不推荐用于严重脓毒血症的病人，以