Anemia and erythropietin in critically ill patientsS. Baginski1
, R. Körner1
, U. Frei1
, K.-U. Eckardt1
1Universitätsklinikum Charité der Humboldt-Universität zu Berlin, Campus Virchow-Klinikum, Medizinische Klinik m. S. Nephrologie und Internistische Intensivmedizin
Die therapeutische Gabe von Blut und Blutkomponenten ist auch heute noch mit potenziellen Nebenwirkungen und Risiken verbunden. Außerdem können Blutkonserven zunehmend nicht mehr in ausreichendem Umfang zur Verfügung gestellt werden. Diese Umstände und die positive Erfahrung der erfolgreichen Behandlung verschiedener Anämieformen mit rekombinantem humanen Erythropoietin (rHuEPO) haben dazu geführt, dass in den letzten Jahren das Interesse an der lange wenig beachteten Anämie des kritisch kranken Patienten stark zugenommen hat. Wie bei der Anämie chronischer Erkrankungen sind die Ursachen der Anämie kritisch kranker Patienten vielfältig: vorbestehende Anämie, Blutverluste, inadäquate endogene Erythropoietinproduktion, verkürzte Erythrozytenlebensdauer, verminderte Eisenverfügbarkeit und eine direkte Hemmung der Erythropoiese durch Zytokine tragen zur Entwicklung dieser Anämie bei. Die Bedeutung der Anämie für Verlauf und Prognose kritisch kranker Patienten ist nicht geklärt, und es gibt bislang keine eindeutigen Empfehlungen für ein optimales Therapiemanagement. rHuEPO hat sich neben Strategien zur Vermeidung von Blutverlusten als attraktive Therapieoption erwiesen, die gegenwärtig in Studien evaluiert wird.
Abstract
The transfusion of red blood cells is still associated with possible adverse effects and a residual risk of transmission of viral and nonviral diseases. In addition, there is an increasing shortage of blood supply worldwide. These two facts together with the success experienced in the treatment of various types of anemia with recombinant human EPO, have recently led to an increasing interest in the anemia of critically ill patients. As in the anemia of chronic diseases there are several reasons that contribute to the development of anemia in patients on intensive care units: pre-existing anemia, blood loss, reduced red cell life span, impaired iron availbility and a direct inhibition of erythropoiesis by inflammatory cytokines. The implications of anemia for the progression and prognosis of critical illness are still unclear and the optimal treatment, including optimal “transfusion triggers” remains controversial. Recombinant human EPO has been proven to be effective in ameliorating the anemia of critical illness in several pilot studies and is currently being tested in larger trials.
2
Anonymous.
European best practice guidelines for the management of anaemia in patients with chronic renal failure.
Nephrol Dial Transplant.
1999;
14 (Suppl 5)
1-50
3
von Ahsen N, Müller C, Serke S, Frei U, Eckardt K U.
Important role of non-diagnostic blood loss and diminished erythropoietic response in anemia of medical intensive care patients.
Crit Care Med.
1999;
27
2630-2639
5
Akahane K, Hosoi T, Urabe A, Kawakami M, Takahu F.
Effects of recombinant tumor necrosis factor (rhTNF) on normal human and mouse hematopoietic progenitor cells.
Int Cell Cloning.
1987;
5
16-26
6
Alazia M, Colavolpe J C, Botti G. et al .
Spoliations sanguiones liees aux prelevements en reanimation: etude preliminare.
Ann Fr Anaesth Reanim.
1996;
15
1004-1007
7
Biemsa D H, Van de Wiel A, Begiun Y, Kraijenhaagen R J, Marx J JM.
Post-operative erythropoiesis is limited by the inflammatory effect of surgery on iron metabolism.
Eur Clin Invest.
1995;
25
383-389
8
Boshkov L K, Tredget E E, Janowska-Wieczorek A.
Recombinant human erythropoietin for a Jehova’s witness with anemia of thermal injury.
Am J Hematol.
1991;
37
53-54
9
Brines M L, Ghezzi P, Keenan S. et al .
Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury.
Proc Natl Acad Sci USA.
2000;
12
10 526-10 531
10
Broxmeyer H E, Lu L, Platzer E, Feit C, Juliano L, Rubin B Y.
Comparative analysis of the influence of human gamma, alpha and beta interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells.
J Immunol.
1983;
131
1300-1305
12
Casadevall N, Nataf J, Viron B, Kilta A, Kiladjian J J, Martin-Dupont P, Michaud P, Papo T, Ugo V, Teyssandier Y, Varet B, Mayeux P.
Pure red cell aplasia and antierythropoietin antibodies in patients treated with recombinant erythropoietin.
New Engl J Med.
2002;
46
469-475
13
Chen H C, Tsai J C, Tsai J H, Lai Y H.
Recombinant human erythropoietin enhances superoxide production by FMLP-stimulated polymorphnuclear leukocytes in hemodialysis patients.
Kidney Int.
1997;
52
1390-1394
15
Corwin H L, Gettinger A, Rodriguez R M, Pearl R G, Gubler D, Enny C. et al .
Efficacy of recombinant human erythropoietin in the criticaly ill patient: a randomized double blind placebo controlled trial.
Crit Care Med.
1999;
27
2346-2350
16
DeMeester S R, Marsh E E, Gerkin T M, Rodriguez J L.
Immediate use of recombinant erythropoietin in a Jehova’s witness following major blunt trauma.
Contemp Surgery.
1994;
45
228-232
20
Ferguson B J, Skikne B S, Simpson K M, Bynes R D, Cook J D.
Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia.
J Lab Clin Med.
1992;
119
385-390
21
Fitzgerald R D, Martin C M, Dietz G E. et al .
Transfusing red blood cells stored in citrate phosphate dextrose adenin-1 for 28 days fails to improve tissue oxygenation in rats.
Crit Care Med.
1997;
25
726-732
22
Fleming R YD, Herndon D N, Vaidya S. et al .
The effect of erythropoietin in normal healthy volunteers and pediatric patients with burn injuries.
Surgery.
1992;
112
424-432
23
Gabriel A, Kozek S, Chiari A, Fitzgerald R, Grabner C, Geissler K. et al .
High-does recombinent human erythropoietin stimulates reticulocyte production in patients with multiple organ dysfunction syndrome.
J Trauma.
1998;
44
363-367
24
Hadfield R J, Sinclair D G, Holudsworth P E. et al .
Effects of enteral and parenteral nutrition on gut mucosal permeability in the critically ill.
Am J Resp Crit Care Med.
1995;
152
1545-1548
25
Hebert P C, Wells G, Tweeddale M, Martin C, Marshall J, Pham B. et al .
Does transfusion practice affect mortality in critically ill patients?.
Am J Resp Crit Care Med.
1997;
155
1618-1623
26
Hebert P C, Wells G, Blajchman M A, Marshall J, Martin C, Pagliarelo G. et al .
A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care.
N Engl J Med.
1999;
340
409-417
28
van Iperen C E, Gaillard C AJM, Kraaijenhagen R J, Braam B G, Marx J JM, Van de Wiel A.
Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients.
Crit Care Med.
2000;
288
2773-2778
29
Jelkmann W, Pagel H, Wolff M, Fandrey J.
Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys.
Life Sciences.
1992;
50
301-308
30
Jongen-Lavrencic M, Peeters H RM, Rozemuller H, Rombouts W JC, Martens A CM, Vreugdenhil G. et al .
IL-6 induced aneamia in rats: possible pathogenic implications for aneamia observed in chronic inflammations.
Clin Exp Immunol.
1996;
103
328-334
34
Koestner J A, Nelson L D, Morris J A, Safcsak K.
Use of recombinant human erythropoietin (r-HuEPO) in a Jehova’s witness refusing transfusion of blood products: case report.
J Trauma.
1990;
30
1406-1408
38
Maury C PJ, Andersson L C, Teppo AM; Partanen S, Juvonen M.
Mechanism of anemia in rheumatoid arthritis: deminstration of raised interlukin 1 beta concentrations in anemic patients and of interleukin 1 mediated suppression of normal erythropoiesis and proliferation of human erythroleukemia (HEL) cells in vivo.
Ann Rheum Dis.
1988;
47
972-978
39
Moghtader J C, Edlich R F, Mintz P D, Zachmann G C, Himel H N.
The use of recombinant human erythropoietin and cultured epithelial autografts in a Jehova’s witness with a major thermal injury.
Burns.
1994;
20
176-177
43
Rogiers P, Zhang H, Leeman M, Nagler J, Neels H, Mélot C. et al .
Erythropoietin response is blunted in critically ill patients.
Int Care Med.
1996;
23
159-162
45 Schönhofer B, Wenzel M, Geibel M, Köhler D. Blood transfusion and lung function in chronically anemic patients with severe chronic obstructive pulmonary disease. Crit Care Med 1998; 1824-1828
46
Smith S N, Milov D E.
Use of erythropoietin in Jehova’s witness children following acute gastrointestinal blood loss.
J Fla Med Assoc.
1993;
80
103-105
48
Still J M, Belcher K, Law E J, Thompson W, Jordan M, Lewis M. et al .
A double-blinded prospective evaluation of recombinant human erythropoietin in acutely burned patients.
J Trauma.
1995;
38
233-236