1、3,170 ml HES,16,905 ml non-HES fluids,=,1,5.3,VISEP Trial (HES vs. Ringers Lactate) - Ratio of HES to non-HES fluids in the HES group (days 0-4) -,Hemodynamic effects,Mean arterial pressure,Central venous pressure,Central venous oxygen saturation,100,75,50,0,% of patients reaching composite goals,25
2、,VISEP Trial (HES vs. Ringers Lactate) - Results IV: Hemodynamic goals (CVP, MAP, ScvO2) -,Effects on renal function,VISEP Trial (HES vs. Ringers Lactate) - Start of intervention -,Diuresis,Days 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21,5000 4500 4000 3500 3000 2500 2000 1500 10005000,
3、ml,Creatinine,Mean SOFA Score,7.53,Mean,Ringers lactate n = 274,3.62,SD,6.75,Median,8.0,Mean,HES n = 262,4.05,SD,7.29,Median,0.8,p,VISEP Trial (HES vs. Ringers Lactate) - Results VII: Morbidity -,VISEP Trial (HES vs. Ringers Lactate) - Results VIII: Morbidity -,Days 0 1 2 3 4 5 6 7 8 9 10 11 12 13 1
4、4 15 16 17 18 19 20 21,100009000800070006000500040003000200010000,HES group,VISEP Trial (HES vs. Ringers Lactate) - Total fluids (ml) -,Ringerslactate,attributable amounts of HES,236 185 149 124 109 114 93 93 80 82 75 67 68 66 53 56 47 48 48 33 34,* Pat. receiving HES,N=*,VISEP: RRT and cumulative d
5、ose of HES or Ringers lactate by various dosage groups,P=0.007 between HES doses P=0.345 between Ringers lactate doses,VISEP Trial (HES vs. Ringers Lactate) - HES 22 ml/kg/BW -,VISEP Trial (HES vs. Ringers Lactate) - HES 22 ml/kg/BW -,57.6%,30.9%,0%,25%,50%,75%,22.8%,33.0%,0%,25%,50%,75%,Mortality (
6、%),n=162,n=100,HES 22 ml/kg BW/day,HES 22 ml/kg BW/day *,n=162,n=99,p=0.071,P0.0001,* on at least one study day,VISEP Trial (HES vs. Crystalloid) - Subgroup mortality HES 22 ml/kg BW/day,Progression of mortality from 28 days to 90 days,HES 22 ml/kg BW/day n=162,HES 22 ml/kg BW/day * n=99,* on at lea
7、st one study day,P 0.0001,VISEP Trial (HES vs. Ringers Lactate) - Survival HES 22 ml/kg/BW -,* on at least one study day,VISEP Trial (HES vs. Ringers Lactate) - Morbidity HES 22 ml/kg/BW -,33.6%,30.9%,0%,25%,50%,75%,24.2%,22.8%,0%,25%,50%,75%,28-day mortality,90-day mortality,Mortality (%),n=256,n=1
8、62,HES,Ringers lactate,n=256,n=162,p=0.747,p=0.562,VISEP Trial (HES vs. Ringers Lactate) - Mortality HES 22 ml/kg/BW vs Ringers lactate -,VISEP Trial (HES vs. Crystalloid) - Subgroup SOFA crystalloid vs. HES 22 ml/kg BW/day -,VISEP Trial (HES vs. Ringers Lactate - Morbidity Ringerslactate vs. HES 22
9、 ml/kg BW/day -,VISEP Trial (HES vs. Crystalloid) - Subgroup morbidity crystalloid vs. HES 22 ml/kg BW/day -,Volume resuscitation with HES 10% (200/0.5) results in faster hemodynamic stabilisation. Acute renal failure and need for renal replacement therapy occurred more often in the HES group 28-day
10、 mortality is not significantly different between study groups 90-day mortality tends to be higher (33.9% vs 41.0% (p=0.11) in the HES group,VISEP Trial (HES vs. Ringers Lactate) - Summary I: univariate analysis -,Increasing cumulative dosages of HES are associated with an increase in 90-day mortali
11、ty. (p=0.0015).Increasing cumulative dosages of HES, but not Ringerslactate are associated with renal failure and renal replacement therapy; independently from baseline creatinine clearance.,VISEP Trial (HES vs. Ringers Lactate) - Summary II: multivariate analysis -,Increasing cumulative dosages of
12、Ringers lactate and HES are associated with an increase in 90-day mortality. This effect is more marked in patients receiving HES (p=0.0015).Increasing cumulative dosages of HES, but not Ringerslactate are associated with renal failure and renal replacement therapy; independently from baseline creat
13、inine clearance.,VISEP Trial (HES vs. Ringers Lactate) - Summary II: multivariate analysis -,HES 10% (200/0.5) can not be recommended for patients with severe sepsis and other patients at risk for the development of acute renal failure.The safety margin for HES is narrow. Exceeding the recommended u
14、pper dose limit (20 ml/kg BW / day) should be avoided.Whether newer HES preparations can be safely used in patients at risk for the development of acute renal failure remains to be elucidated.,VISEP Trial (HES vs. Ringers Lactate) - Conclusions -,After the results of the VISEP trial were available i
15、.e. Feb.1st 2006 we stopped the use of HES 130/0.4 (Voluven) and replaced it by succinylated gelatin 4%,Impact of change in type of colloid HES 6 %, 130/04 vs. succinylated Gelatin 4% on resource use & costs,Time period Price per Unit Time periodFeb. 1st, 2005 Feb. 1st, 2006 -June 15th, 2005 June 15
16、th, 2006 Colloid used (units/per 500 ml) Gelatin 4% 77 2.85 3237HES 10% 200/0.5 117 61HES 6% 130/0.4 4545 3.99 29 Costs for HES 6% 17,886 115 Costs for Gelatin 4% 219 9,225 Total Costs 18,105 9,340 Cost savings in observation period: 8475 Cost savings per year: 23,373 ,Association between change in
17、type of colloid & patient morbidity/mortality - HES 6% 130/0.4 vs. Gelatin 4%,Time period Time period p-valueFeb. 1st, 2005 - Feb. 1st, 2006 -June 15th, 2005 June 15th, 2006 Patients n= 1424 1580 m/f % 65/35 64/36 Age yrs. 62.25 62.26 0.735 SOFA-Score (mean) 4.92 5.28 0.004 SAPS-Score (mean) 30.81 3
18、3.84 0.000 Creatinine at admission (mg/dl) 1.23 1.22 0.060 CRP at admission 45 41 0.022 ICU-mortality (%) 6 (n=83) 6 (n=93) Creatinine at discharge (mg/dl) 1.18 1.14 0.053 Patients RRT (%) 6 (n=81) 5 (n=86) Time on RRT (hrs) 131 109 0.990 Length of ICU-stay (days) 5.27 4.73 0.657,Allergic reactions
19、attributable to Gelantin (3237 units) three,Messmer 6: 10000,Laisner 35: 10000,Zander R et al. AINS 2005; 40: 701-719,Evidence-based colloid use,Evidence-based colloid use in the critically ill: ATS Consensus Statement. Am J Respir Crit Care Med 2004,Colloids should be administered first in nonhemor
20、rhagic shock resuscitation (III) HES solutions should be used with caution in cardiopulmonary bypass (meta-analysis) and in patients with sepsis (II-A) Colloids should be avoided or used with caution in patients with traumatic brain injury (I),Grades of evidence obtained from I at least one properly
21、 randomized controlled trial II-A well-designed controlled trials w/o randomization or RCTs w/o blinding II-B well-designed cohort or case-control analytic studies II-C multiple time series, uncontrolled cohort studies, and case series III Expert opinion,German Sepsis Society,www.sepsis-gesellschaft
22、.de,Sepsis and multiorgan dysfunction,3nd International Congress,Weimar, 05.- 08. September 2007,CME Certified Education 30 points,Thank you for your attention !,Effects on coagulation,Platelet count,HES induced coagulopathy,- Acquired von Willebrand sydrome 1 - Prolongation of partial and activated
23、 partial thromboplastin time1,4Inhibition of the functional receptor for fibrinogen on the platelet surface (glycoprotein IIa-IIIb) 2 - Factor VIII:C and platelet aggregation significantly lower in comparison with albumin 3 - Decrease in fibrinogen levels 5Compromised clot polymerisation 6 - Increas
24、ed bleeding complications,1 De Jonge et al, Intensive Care Med 2001; Jonville-Bera et al, NEJM 2001 2 Stgermller et al, Anesth Analg 2000; 3 Omar et al, Clin Biochem 1999 4 Treib et al, Arzneimittelforschung 1997; 5 Ruttmann et al, Br J Anaesth 1998; 6 Entholzner et al, Acta Anaesthesiol Scand 2000,
25、HES and hemostasis,Kozek-Langenecker et al, Anesthesiology 2005,CO: Subendothelial collagen GAC: Glycaminoglycans Fg: Fibrinogen,Rapidly degradable HES solutions have minimal influence, if any, on hemostasis.“,Plasma clotting does not differ in different HES solutions in vitro,Nielsen et al, Acta An
26、esth Scand 2005,Values are expressed as mean + SD. Normal: no dilution; NS: 0.9% NaCl; ALB: 5% human albumin; HEX: Hextend (HES 670/0.75); PENT: PentaLyte (HES 220/0.45); VOL: Voluven (HES 130/0.4). R: reaction time (s); : alpha (); A: amplitude (mm); G: shear elastic modulus (dynes/cm2); MTG: maxim
27、um thrombus generation (dynes/cm2/ s); TTG: total thrombus generation (dynes/cm2).*P 0.05 vs. normal,P 0.05 vs. NS,P 0.05 vs. ALB,P 0.05 vs. PENT.,HES 130/0.4 significanty inhibits platelet function ex vivo,Scharbert et al, Anesth Analg 2004,N=40 adult chronic pain patients scheduled for peridural b
28、lockades Prospective, double-blind, crossover design 6% HES 130/0.4 vs. 6% HES 200/0.5 (control: Ringers lactate) Measurement: Platelet function analyzer (PFA) closure times Results: Both HES 130/0.4 and HES 200/0.5 signficantly prolonged ADP- and Epinephrine induced PFA times. Ringers lactate had n
29、o effect. Dotted lines depict range of normal.,In vitro dilution with different HES solutions,Entholzner et al, Acta Anaesthesiol Scan 2000,C= undiluted control, S: Sodium chloride, *P0.05 vs. Control, #P0.05 vs. Sodium chloride,Extrinsic activated thrombelastography Intrinsic activated thrombelasto
30、hraphy,Effects on tissue storage,Postmortem tissue storage in 10 ARDS patients,Lukasewitz 1994, from: Frster et al: J Ansth Intensivbehandlg 1997,HES storage in skin histiocyte,Reimann et al, DMW 2000,HES storage in nerve cell,Metze et al: Br J Dermatol 1997,HES-induced pruritus in the ICU,Sharland
31、et al, Anaesthesia 1999,Study design: Retrospective survey by postal questionnaire and telephone follow-up Patients and Drugs: 100 patients with an ICU LOS 24 hrs 10% HES 200/0.5 Results: n = 73 patients 34% experienced pruritus since discharge, 44% of these experienced severe, persistent pruritus u
32、nresolved by conventional treatment. Duration up to 1 year after ICU stay Cumulative dose ranged from 0 (n=3) to 27.35 litres (median 2 litres) infused over a median of 2 days (range 1-21 days) Occurrence of pruritus was signficantly related to volume of HES (p=0.003),Foamy macrophage syndrome due t
33、o HES 6 %,Auwerda et al, Ann Intern Med 2002,Patient: 38 yr old woman, plasmapheresis since 1997 because of IgG monoclonal gammopathy, performed initally with gelatin and albumin, since 1999 with HES 6% at a 1:1 ratio Clinical symptoms: Development of severe weight loss (BMI 17.6), sensory polyneuro
34、pathy of the legs, deteriorating eyesight, hepatosplenomegaly with ascites, normocytic anemia (Hb 7.1), thrombocytopenia (121,000), low serum creatinine (40 mol/L) and albumine (26g/L). MRI: vasculitis of the choroid plexus with hydrocephalus and pituitary stalk edema Histology: foamy macrophages in
35、 bone marrow, skin, duodenal mucosa, liver, peritoneum, dura mater and ascites Immunoelectron microscopy with anti-HES antibodies: massive tissue storage of HES, especially in macrophages,Foamy macrophage syndrome due to HES 6%,Auwerda et al, Ann Intern Med 2002,Light microscopy: Bone marrow infiltr
36、ation with CD68+ foamy macrophages (x200, left) Immunoelectron microscopy: Endothelial cells (A) and histiocytes (B). HES-antibody staining reveals typical HES+ bodies in vacuoles (x2200, right) prepared by Dr. Stnder, Mnster,Ginz et al, Anaesthesist 1998,Kidney: Osmotic nephrosis of proximal tubular cells containing colloid material, x600,Colloid storage in lung, liver, spleen and kidneys in a patient with sepsis and MOD,
