Bluttransfusionen in der Intensivstation. Von der Physiologie zur Cost-Effectiveness. GR. Kleger, MIPS, ST. Gallen

Transkript

1 Bluttransfusionen in der Intensivstation Von der Physiologie zur Cost-Effectiveness GR. Kleger, MIPS, ST. Gallen

2 % GDP Bluttransfusionen in der IPS: USA Switzerland Germany France Italy Great Britain

3 3 MIPS 2007 Eintritte 1090 Aufenthaltsdauer 2.3 d Pflegetage: 2986 EK (leukozytendepl) 615 davon 71 bestrahlt Kosten / EK SFr Kosten 2007: SFr

4 original review editorial

5 5 Bluttransfusionen in der Intensivstation von der Physiologie zur Cost Effectiveness Epidemiologie Physiologie Efficacy, Effectiveness Cost-Effectiveness

6 6 Epidemiologie (Quelle: America s Blood Centers, Patienten/y werden in den USA transfundiert Erythrocytenkonseven/d 1 von 7 Spitaleintritte braucht Blut 30-50% der IPS-Patienten werden transfundiert (case mix) 13 Tests (11 bez. Krankheitserreger) werden mit jeder Konserve durchgeführt Intensivstationen gehören zu den grössten Blutverbrauchern Vincent JL. Anemia and blood transfusions in the critically ill patients. JAMA 2002: 288; 1499 Groeger JS. Descriptive analysis of critical care units in the United States patient characteristicsand intensive care unit utilization. Crit Care Med 1993; 21: 229 Corwin HL. RBC transfusion in the ICU is there a reason? Chest 1995; 108: 767 mehr als 2/3 der Transfusionen in Intensivstationen sind nicht mit akutem Blutverlust verbunden Corwin HL. RBC transfusion in the ICU is there a reason? Chest 1995; 108: 767

7 7 Variable Transfusionsschwellen (TS) Canadian survey 1992 Transfusionsschwelle 9 g/dl: 35 % Transfusionsschwelle 10 g/dl: 40 % Streubreite 5-12 g/dl Universitäre Zentren haben TS signifikante individuelle, institutionelle und regionale Variabilitäten der TS Hébert PC. A survey of red cell transfusion practices in canadian critical care practioners. Clin Invest Med 1994

8 8 Variable Transfusionsschwellen (TS) Corwin HL. Crit Care Med 2004; 288:

9 Transfusion rates vary significantly amongst Canadian medical centres 9 Hutton B. Can J Anesth 2005; 52: 581

10 Epidemiologie: Anämie in der Intensivstation vorbestehende Anämie (anemia of chronic diseases) Vincent JL. Anemia and blood transfusions in the critically ill patients. JAMA 2002: 288; 1499 häufige Blutentnahmen (point of care testing) Vincent JL. Anemia and blood transfusions in the critically ill patients. JAMA 2002: 288; 1499 Mikroblutverluste im Intenstinaltrakt Blutverluste durch interventionelle Therapien inadäquat niedrige Erythropoietinkonz. Rodriguez RM. Nutritional deficiencies and blunted erytropoietin response as cause of the anemia in critical.illness. J Crit Care 2001; 46: 36 Hobisch-Hagen P. Blunted erytropoietic response to anemia in multiple trauma patients. Crit Care Med 2003; 29:743 Rogiers P. Erythropoietic response is blunted in critically ill patients: Intensive Care Med 1997: 23; 159 Krafte-Jacobs B. Erythropoietin response to critical illness. Crit Care Med 1994; 22: 821 Von Ahlsen N. Important role of nondiagnostic blood loss and blunted erythropoietic response in the anemia of medical intensive care patients. Crit Care Med 1990; 27: 2630 Ansprechen der KM-Stammzellen auf Erythropoietin Corwin HL. Efficacy of recombinant human erythropoietin in the critically ill patient: a randomized, double blind placebo controlled trial. Crit Care Med 1999; 27: 2346 Corwin HL. Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. JAMA 2002; 288: 2827 Gabriel A. A high dose recombinant human erythropoietin stimulates reticulocyte production in patients with multiple organ dysfunction syndrome. Trauma 1998; 44: 361 funktioneller Eisenmangel van Iperen CE. Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients. Crit Care Med 2000; 28: 2773 Weiss G. Linkage of cell-mediated immunity to iron metabolism. Immunol today. 1995; 15: 74 10

11 11 course of hemoglobin patterns by admitting Hb level category Vincent, J. L. et al. JAMA 2002;288:

13 13 O 2 -Transport (O 2 -Delivery) DO 2 = CO x CaO 2 CaO 2 = SaO 2 x Hb x pao 2 x DO 2 = (SaO 2 x Hb x pao 2 x 0.003) x CO

14 14 O2-Extraktion b. O2-Transport

15 15 supranormaler DO 2 Shoemaker WC. Role of oxygen dept in the development of organ failure, sepsis and death in high risk surgical patients.chest 1992; 102:

16 16 O 2 -Transport: SaO 2

17 17 Viskosität und O 2 -Transport Messmer KFW in Le point sur la transfusion autologue. Arnette, Paris pp

18 18 Mikrozirkulationsstörungen Messparameter d1 d14 d28 ph ,3, DPG mmol/l ATP mmol/l visk Viskosität (D150) mpa Mansouri Taleghani B. in Transfusionsmedizin 1995/96. Karger 1996; 33:

19 Mikrozirkulationsstörungen 19 Erythrocytenkonzentrat: Tag 0

22 Mikrozirkulationsstörungen 22 old red blood cells fresh red blood cells Fitzgerald RD. Transfusing red blood cells stored in citrate phosphate dextrose adenine-1 for 28 days fails to improve tissue oxygenation in rats. Crit Care Med 1997; 25:

23 23 intestinale Perfusion Grays Anatomy 36 th edition Churchill Livingstone 1980

24 Mikrozirkulationsstörungen 24 Marik PE. Effects of stored-blood transfusions on oxygen delivery in patients with sepsis. JAMA 1993; 269:

25 25 Immunsuppression durch EC-Transfusion gesteigerte Transplantatüberlebensrate nach TX (Niere) Opelz G. Prospective evaluation of pretransplant blood transfusion in cadaver kidney recipients. Transplantation 1997; 63: Frührezidive bei Colo-Rectalen Karzinomen postoperative Infekte

26 26 Immunsuppression durch EC-Transfusion Cancer Variable Reference Colorectal 5ys-df Burrows L. Cancer Det Prev 1987 Colorectal 5ys-df, 5ys Blumberg N. Br Med J 1985 Colorectal 5ys Foster RS. Cancer 1985 Colorectal 5ys Corman J. Can J Surg 1986 Colorectal 5ys-df Parrott NR. Br J Surg 1986 Colorectal 5ys Voogt PJ. Cancer 1987 Colorectal s, dfs Stephenson KR. Ann Surg 1988 Gastric 5ys Kaneda M. Transfusion 1987 Lung 5ys-df Tartter PL. J Th Card Surg 1984 Lung 5ys Hyman NH. Am J Surg 1985 Breast 5ys-df Tartter PL. Surgery 1985

28 critical care and erythrocyte transfusion exc. Kinder 5 pages 68 articles original 18 review 34 retrosp. obs 3 cross sect. 8 prosp. obs. 5 prosp. rand. 1 ce 1 systematic 4 non system. 30 editorial/letter 12

29 29 Hb und Mortalität Fallkontrollstudie an 4470 Patienten Patienten die in der Intensivstation versterben haben einen Niedrigen Hb-Wert 95 ± 26 vs. 104 ± 23 g/l und werden häufiger transfundiert 42.6% vs 28.0% Hébert PC. Does transfusion practice affect mortality in critically ill patients. Am J Resp Crit Care Med 1997; 155:

30 30 kardiovaskuläre Mortalität Fallkontrollstudie an 4470 Patienten Mortalität aufgeschlüsselt bezüglich Patienten mit oder ohne kardiovaskuläre Erkrankungen Bei Patienten mit kardiovaskulären Krankheiten war ein Trend Höherer Mortalität bei Hb < 95 g/l (55 vs. 42 %, p = 0.009) Reduktion der Mortalität (OR 0.8 pro 10 g/l Hb ) Hébert PC. Does transfusion practice affect mortality in critically ill patients. Am J Resp Crit Care Med 1997; 155:

31 kardiovaskuläre Mortalität Fallkontrollstudie an 4470 Patienten Stratifizierung nach APACHE, Hb vor Transfusion und Anzahl transfundierter Ec-Konzentrate und kardiovaskulären kardiovask. KrankheitKrankheiten Bei Patienten mit APACHE II > 20 und kardiovask. Krankheit wird eine Reduktion der Mortalität bei Transfusion von EK beobachtet Hébert PC. Does transfusion practice affect mortality in critically ill patients. Am J Resp Crit Care Med 1997; 155:

32 32 kardiovaskuläre Mortalität Resultate: Reduktion der Mortalität nur in der Patientengruppe mit Anämie & cardiovaskulären Erkrankungen, & APACHE >20 keine Reduktion der Mortalität (evt. ) in allen anderen Patientengruppen unabh. vom Schweregrad der Erkrankung Hébert PC. Does transfusion practice affect mortality in critically ill patients. Am J Resp Crit Care Med 1997; 155:

33 33 Sepsis: early goal directed therapy Rivers E. N Engl J Med 2001; 345: 1368

34 34 Sepsis: early goal directed therapy Rivers E. N Engl J Med 2001; 345: 1368

35 35 supranormaler DO 2 Shoemaker WC. Role of oxygen dept in the development of organ failure, sepsis and death in high risk surgical patients. Chest 1992; 102:

36 36 Ist supranormaler DO 2 -Transport sinnvoll? Gattinoni L. A trial of goal-oriented hemodynamic therapy in critically ill patients. New Engl J Med 1995; 333:

37 37 Ist supranormaler DO 2 -Transport sinnvoll? outcome at 6 mt Gattinoni L. A trial of goal-oriented hemodynamic therapy in critically ill patients. New Engl J Med 1995; 333:

38 38 Ist supranormaler DO 2 -Transport sinnvoll? Heyland DK. Maximizing oxygen delivery in critically ill patients: A methodologic appraisal of the evidence. Crit Care Med 1996; 24:

39 39 Transfusionsschwelle

40 40 Transfusionsschwelle prospektive, randomisierte, kontrollierte Studie 838 kritisch kranke Patienten (Hb < 9 g/dl, 72 h) chirurgische und internistische Patienten inkl. KHK Gr. 1: Transfusionsschwelle = Hb 7.0 g/dl Gr. 2: Ziel-Hb 7-9 g/dl Transfusionsschwelle = Hb 10.0 g/dl Ziel-Hb g/dl endpoint: Mortalität Subgruppenanalyse: Alter < 55 y, APACHE < 20, Patienten mit Herzkrankheit

41 Transfusionsschwelle? 41 Hébert PC. A multicenter, randomized, controlled clinical trialof transfusion requirements in critical care. N Engl J Med 1999; 340:

42 42 Transfusionsschwelle? Hébert PC. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999; 340:

43 43 logistic regression on mortality Vincent, J. L. et al. JAMA 2002;288:

44 44 difference in mortality by number units transfused Vincent, J. L. et al. JAMA 2002;288:

45 45 survival analysis, matched by propensity scores Vincent, J. L. et al. JAMA 2002;288:

47 47 Kostentreibende Faktoren Zunehmendes Patientenalter Chronische Krankheiten (acute disease controlled) Exponentielle Entwicklung neuer Technologien

48 Health Costs Bluttransfusionen in der IPS: 48 Law of diminishing returns Cost-health-ratio Intensity of Health Services

49 Health Bluttransfusionen in der IPS: 49 Law of diminished return Δ Health Δ Health Δ Costs Δ Costs Resource use (Costs)

50 50 Cost-effectiveness ratio an incremental ratio Ratio of change in costs (incremental costs) divided by change in effects (incremental effects) CE Ratio = Cost treatment - Cost placebo Effect treatment - Effect placebo where Cost = all costs (not just drug acquisition costs) Example of ratios Δ$ per Δ survivor Δ per Δ pneumonia prevented Δ per Δ quality-adjusted life year (QALY)

51 Difference in Costs (US$) Bluttransfusionen in der IPS: 51 Cost-effectiveness Plane 50 40k 30k More costly Less effective JUST SAY NO More costly More effective 20k 10 k 0-10k -20k Less costly Less effective Less costly More effective JUST SAY YES - 30k Difference in Effects (QALY)

52 cost-benefit and erythrocyte transfusion 20 biotechnology a. Periop. 20 allg. 11 cell saver 8 erythropoetin 1 3 pages 53 articles 33 articles IPS 5 chro. anemia Others 5 epo 5 Erw. 1 Neonat.1 Politics 3

53 Difference in Costs (US$) Bluttransfusionen in der IPS: k 30k 20k 10 k 0-10k -20k - 30k More costly Less effective JUST SAY NO Hb >7g/L & - Ø ak Blutung - Ø ACS - Ø septic shock Less costly Less effective More costly More effective Hb 9.5 resp. 10 g/l ACS resp early sepsis Hb = 7 g/l ausser -Ø ak. Blutung - ACS -early septic shock Less costly More effective JUST SAY YES Difference in Effects (QALY) 2

54 54 Laufende Studien ( A service of the U.S. National Institute of health Randomized trial of liberal (Hgb 10g/L) vs. restrictive (Hgb < 70 g/l) transfusion strategy in elderly cardiac surgery patients ((70-90 y, non emergency ACB, postoperative Hgb g/l A prospective randomized controlled trial comparing the effects of fresh (<5 d stored) vs. old (>5 d stored) blood on cerebral oxygen extraction in patients with traumatic brain injury The israeli trigger for blood transfusions in the ICU (observational) NIRS as transfusion indicator in neurocritical patients (randomized, open label) Conservative vs. liberal red cell transfusion in myocardial infarction trial: The CRIT pilot (within 72 h of AMI)

55 55 References tpa for AMI Statins Air bags CABG for 2V disease Implantable defibrillators Warfarin for stroke prophylaxis Drotrecogin for sepsis $15,000 $164,000 $32,000 $143,000 $24,000 $61,000 $8,000 $69,000 $37,000 $74,000 $8,000 $370,000 $26,700 $48,800 $20k/QALY $100k/QALY