羥乙基淀粉 vs. 晶體液治療膿毒血癥和感染性休克患者-德國 SepNet VISEP 試驗結果(英文)1課件

1、G. Marx, MD麻醉/ICU科,Friedrich-Schiller-大學, 耶拿德國羥乙基淀粉 vs. 晶體液治療膿毒血癥和感染性休克患者-德國 SepNet VISEP 試驗結果ICU teamICU manager7 ICU-Consultants28 ICU registrars200 ICU nursesICUICU of tomorrowNew IT concepts established50 surgical ICU bedsEpidemiologyMost frequent causes of death in Germany 20038Federal Agency f

2、or Statistics PrevalenceStudy SepNet 200392.67364.22959.34459.11739.28637.57920.8885.739Prevalence and incidence estimatesSepsisSevere sepsis / septic shockTotalPatients in German ICUs(per day)1.7421.5453.287Mean duration of disease(days)9,28,5New cases(per year)79.00075.000154.000Deaths(per year)20

3、.00040.00060.000German Prevalence Study 2003Mortality54%HospitalICUp = 0,004German Prevalence Study 2003 * 454 ICUs (310 hospitals) representative for 1380 hospitals (490.000 beds), 2.075 ICUs (19.000 beds)Treatment costs for sepsis- Intensive care units of three university hospitals -(Jena, Gttinge

4、n, Halle)n = 388 ICU-days 16.6Mortality 42.6% Hospital-days 32.5per patientper dayAverage treatment costs25,695 1,454 Survivors24,014 1,269 Non-survivors28,503 1,848 Moerer O et al.,Intensive Care Med 2002; 28: 1440-1446. Volume replacementDelayed treatment = increased mortality: diagnosis, diagnosi

5、s, diagnosis, Start of treatmentICUBurden of organ dysfunctionPrognosisPre-hospital ED WardDelay in diagnosisDellinger, et. al. Crit Care Med 2004, 32: 858-873. Fluid resuscitation in severe sepsis and septic shock: An evidence-based reviewFluid resuscitation may consist of natural or artificial col

6、loids or crystalloids. There is no evidence-based support for one type of fluid over anotherFluid challenge in patients with suspected hypovolemia may be given at a rate of 500-1000 mL of crystalloids or 300-500 mL of colloids over 30 mins & repeated based on response (increase in blood pressure & u

7、rine output) & tolerance (evidence of intravascular volume overload)Vincent JL, Gerlach H. Crit Care Med. 2004 ;32(11 Suppl):S451-4.Preferred plasma volume expanders for critically ill patients: results of an international surveyCRYCO Study group515 ICUs 75 item questionaireSchortgen F et al. Intens

8、ive Care Med 2004; 30: 2222-29Preferred 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 questionaire%Preferred plasma volume expanders for critically ill patients: results

9、of an international survey%Schortgen F et al. Intensive Care Med 2004; 30: 2222-29A comparison of albumin and saline for fluid resuscitation in the ICURCT6997 PatientsControl group: N-Saline Study group: 4% Albumin Finfer S et al. N Engl J Med 2004;350:2247-56A comparison of albumin and saline for f

10、luid resuscitation in the ICUProbability of Survival0,5028AlbuminN-Saline1,0 Finfer S et al. N Engl J Med 2004;350:2247-56Dubios MJ et al. Crit Care Med 2006; 34: 2536-2540Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled

11、, pilot study * P= 0,026VISEP studyData Center University of LeipzigCoordination Center University of JenaSample Bank University of JenaRegional Study CentersSepNet Structure B.Braun, Melsungen, GermanyMain sponsorHemocue, Groostheim, Germany Novo Nordisk, Mainz, GermanyBMBF (Ministry for Education

12、& Research, Germany)1,500 000 VISEP Trial (HES vs. Crystalloid) - Acknowledgments -VISEP Trial (HES vs. Crystalloid) - Patient enrolment per site -Hemohes 10% Fa. B. Braun (HES 200 / 0.5)Hydroxyethyl starch mean molecular weight 200 000Degree of substitution 0.45-0.55C2/C6 ratio 6:1Manufacturers rec

13、ommended maximal daily dose 20 ml / kg BW per day 2.0 g / kg ( 1,500 ml per day for a 75 kg patient)Volume efficacy 130-150%Volume effect: medium (3-4 hours)Volume therapy - HES Characteristics -Dieterich H-J.: J Trauma 2003Reduction of capillary leakage and tissue edemaDecreased tissue injury after

14、 ischemic reperfusionPreservation of gastric-mucosal blood flow and pHiLower incidence of pulmonary edemaDecreased endothelial activation and leucocyte endothelial cell interactionImproved microcirculatory flow and reduced leucocyte adhesionPotential Beneficial Effects of HESSchortgen F. et al. Lanc

15、et 2001;357:911-916However: Renal failure and HESPopulation without renal failureDaysN=64N=65P=0.018Even if regulatory agencies and pharmaceutical companies do not seem to be interested in responding to this important question, international researchers should try to obtain such an answer. Indeed,ne

16、w starches are or will be proposedin the future, and there is presently noproof that they are devoid of the same renal effects.Are we sure that these lesions do not frequently occur in patients with renal diseases, renal ischemia, and incritically ill patients? Riou B et al. Intensive Care Med (1999

17、) 25: 1340 HES is HES Observation 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 1998)1 dayAllison et al. (J Trauma 1999)3 daysKum

18、le 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 days; FU 3 days after infusion Neff et al. (Anest

19、h Analg 2003)Observation periodAuthor28-day mortality reduction by 10%mean SOFA-score reduction by 1.2 pointsVISEP Trial (HES vs. Ringers Lactate) - Primary endpoints - Hydroxyethyl starch (HES): Hemohes 10%, B. Braun Melsungen, Germany Ringers lactate: Sterofundin Fa. B. Braun Melsungen, GermanyFre

20、quency of acute renal failureTime to hemodynamic stabilizationFrequency of treatment with vasopressors (days)Differences in mean SOFA subscoresFrequency of bleeding eventsDuration of mechanical ventilation (days)ICU length of stay (days)90-day mortality VISEP Trial (HES vs. Ringers Lactate) - Second

21、ary endpoints -Severe sepsis and septic shock within 24 hrs after onset (12 hours in ICU acquired severe sepsis/septic shock) VISEP Trial (HES vs. Ringers Lactate) - Inclusion criteria -Age 1000 l HES 24 h prior to randomization,Severe acute or chronic renal dysfunction (previously known creatinine

22、concentration 320 mol/L or a need for dialysis);Intracranial bleedingSevere head trauma with edema,FiO2 at randomization 0,7,Heart failure (NYHA IV),Immunosuppression,DNR-order,Expected survival 28 daysVISEP Trial (HES vs. Ringers Lactate) - Exclusion criteria -Central venous pressure 12 mmHgmean ar

23、terial pressure 70 mmHgcentral-venous O2-saturation 70% Measurements :day 1: 1, 2, 4, 6, 8, 12 hday 2-4: every 12 hday 4: every 24 h VISEP Trial (HES vs. Ringers Lactate) - Hemodynamic goals -600 Randomized297 Assignedto HES 303 Assignedto Ringers lactate27 No informed consent34 No informedconsent1

24、Violation ofelegibility criteria1 Violation ofelegibility criteria262 ITT275 ITTVISEP Trial (HES vs. Ringers Lactate) - Patients in the study -N=53724h12hRandomisationRecruitmentVolume replacement using crystalloids (Sterofundin)Volume replacement using colloids until upper limit (20 mL/kgBW) (HES)D

25、ay21PreICUOnICUVISEP Trial (HES vs. Crystalloid) - Study Flow Sheet -55.014.456.853.012.954.4SAPS II20.06.720.619.06.520.3APACHE II67.013.364.468.014.164.9AgeMedianSDMeanMedianSDMean HESn = 262Ringers lactaten = 275VISEP Trial (HES vs. Ringers Lactate) - Baseline I -3.8104.412Echocardiography (TTE or TEE)24.16324.467PICCO5.0136.618PA-CatheterHemodynamic monitoring24.16326.568ScvO2 70%31.38231.180MAP 70 mm HG21.05519.851CVP 8 mm Hg5.31410.930Chronic renal failure without dialysis6.51711.632Heart failure NYHA II-III30.58030.28