EPO EN CIRUGÍA. Enrique Fernández Mondéjar Unidad de Cuidados Intensivos Hospital de Traumatología Hospital Universitario Virgen de las Nieves Granada

Transcripción

1 EPO EN CIRUGÍA Enrique Fernández Mondéjar Unidad de Cuidados Intensivos Hospital de Traumatología Hospital Universitario Virgen de las Nieves Granada

2 Condiciones Para El Empleo De Un Producto Responde a una necesidad clínica? Es eficaz? Es seguro? El coste es asumible? Comparación con el mejor tratamiento hasta la fecha Determinar: se puede hacer vs se debe hacer

3 Necesidad Clínica (EPO En Cirugía) Reducir el número de trasfusiones Menos complicaciones Mejor pronóstico Anemia Previsible

4 Riesgos de las Trasfusiones Alogénicas

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7 Hebert PC et al NEJM 1999

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9 Vincent et al, Anesthesiology 2008

10 Transfusión? Los riesgos conocidos de las transfusiones han inducido a extremar las precauciones Leucodeplección es actualmente la norma (Los leucocitos han sido implicados en gran parte de los efectos adversos: TRALI, Inmunosupresión) - Otros Balance riesgo/beneficio: Protocolos estrictos: Restricción de trasfusiones Tema abierto?

11 Objetivo: Reducir el nº de trasfusiones alogénicas Donación autóloga preoperatoria Reinfusión intra y/o postoperatoria Hemodilución normovolémica Substitutos de la sangre EPO Combinaciones de varios

12 Substitutos de la sangre

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16 Substitutos de la sangre Por ahora no hay indicación clínica Campo de investigación!!

17 EPO

18 Objetivo: Reducir el nº de trasfusiones

19 Cirugía Ortopédica

20 Cirugía Ortopédica (Cadera y Rodilla) Evolución de Medidas de ahorro de sangre Año 2002 Año 2007 Donación Preop Autóloga: 10% Donación Preop Autóloga: 10% EPO: 30% EPO: 60% Uso Postop. de recuperadores: 11% Uso Postop. de recuperadores: 50% Horstmann WG et al. Arch Orthop Trauma Surg. 2009,

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22 Número de pacientes: 46 (23 por grupo) Grupo I: EPO preoperatoria Grupo II: Extracción de 2 uds Htíes No diferencias estadísticamente significativas!! Seguimiento: 5 días tras la IQ

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32 Cirugía cardiaca

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37 Cirugia de Colon

38 Pre and peri-operative erythropoeitin for reducing allogeneic blood transfusions in colorectal cancer surgery. Editorial group: Cochrane Colorectal Cancer Group. Publication status and date: New, published in Issue 1, Background Patients with colorectal cancer are frequently anaemic and many receive allogeneic red blood cell transfusions peri and post-operatively. Transfusions are accompanied by complications and may increase the rate of recurrence in patients who have a colorectal resection. Recombinant erythropoietin was first used in dialysis patients and more recently in orthopedic surgery to facilitate autologous transfusions. Erythropoietin levels are thought to be lower in cancer patients and erythropoietin is widely used in chemotherapy to treat anaemia and improve quality of life. There may be adverse events associated with its use. Several studies have investigated erythropoietin in colorectal cancer surgery. Objectives The primary objective of this systematic review was to evaluate the efficacy of erythropoietin pre and peri-operatively, in reducing allogeneic blood transfusions in patients undergoing colorectal cancer surgery. Secondary objectives were to determine whether pre and peri-operative erythropoietin improves hematologic parameters (hemoglobin, hematocrit and reticulocyte count), quality of life, recurrence rate, and survival, without increasing the occurrence of thrombotic events and the peri-operative mortality. Search strategy A literature search was performed using MEDLINE, EMBASE, abstracts from the annual meetings of the American Society of Clinical Oncology and the American Society of Colon and Rectal Surgeons until May Selection criteria Randomized controlled trials of erythropoietin versus placebo or no treatment/standard of care were eligible for inclusion. The study must have reported one of the primary or secondary outcomes and included anaemic patients undergoing surgery for colorectal cancer. Data collection and analysis The methodological quality of the trials was assessed using the information provided. Data were extracted and effect sizes were estimated and reported as relative risks(rr) and mean differences (MD) as appropriate. Main results Four eligible studies were identified of ten retrieved in full. There were no statistically significant differences in the proportion of patients transfused between the erythropoietin group and control group. One of the studies showed a small difference in the median number of units transfused per patient favouring treatment. Reporting of hematologic parameters was varied however, there is no evidence for clinically significant changes. There were no significant differences in post-operative mortality or thrombotic events between groups. No included study evaluated recurrences, survival, or quality of life. Studies were of fair methodologic quality and the overall sample size was small therefore results should be interpreted with caution. Authors' conclusions There is no sufficient evidence to date to recommend pre and peri-operative erythropoietin use in colorectal cancer surgery.

39 EPO en cirugía ortopédica: - Reduce la necesidad de transfusión frente a placebo - En pacientes que se anemizan en un programa de donación autologa

40 EPO En Pacientes Críticos

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42 Silver M CCM 2006

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52 EPO en Cirugía de Pacientes Críticos En pacientes críticos: No Subgrupo de Trauma?

53 SEGURIDAD

54 Seguridad Estudios en Pacientes renales Estudios en Pacientes con Cáncer Estudios en Cirugía: centrados en disminución de trasfusiones Poco énfasis en Seguridad

55 Experiencia con Anemia en Quimioterapia Estudios iniciales: Alta eficacia!! Reduce el número de transfusiones Es ese el objetivo? Estudios posteriores: Aumento de Mortalidad!! Cancer maxilofacial(henke et al Lancet 2003) Cancer de mama (Leyland-Jones et al J Clin Oncol 2005) Cancer de pulmón (Wright et al J Clin Oncol 2007), Cancer maxilofacial (Goldberg et al Cancet Letter 2007) Cancer linfoproliferativo y cancer no mieloide (

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59 Causas? Aumento de la Hb Cambios reológicos secundarios a las variaciones de la Hb Efectos tróficos en el endotelio vascular Cáncer: Posible incremento del crecimiento del tumor?

60 Sotwell PS et al. Spine, 2009

61 Sotwell PS et al. Spine, 2009

62 Sotwell PS et al. Spine, 2009

63 Sotwell PS et al. Spine, 2009

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65 Riesgo / Beneficio (Perioperatorio) Transfusión EPO

66 El coste es asumible?

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70 Condiciones Para Un Producto Responde a una necesidad clínica? Es eficaz? Es seguro? El coste es asumible? Comparación con el mejor tratamiento hasta la fecha

71 Empleo de EPO (Eficacia y Seguridad) EPO puede disminuir la necesidad de trasfusión en algunos grupos de pacientes Seguridad 100%?:!!Hay que utilizarla Seguridad < 100%?: Comparación con la mejor estrategia conocida

72 Volume 43, April 2003 TRANSFUSION

73 Trasfusión alogénica: - El 10% con Hb superior a 13gr%!! - El 27% con Hb entre 10 y 10,9 gr%!!

74 Trasfusión vs EPO Trasfusión EPO Pacientes en riesgo: Pacientes en riesgo: % Riesgos 100% EPO incrementa el nº de fenómenos trombóticos Otros riesgos? Comparar: - Morbi mortalidad y riesgos de las trasfusiones - Morbi mortalidad y riesgo de la EPO

75 Necesidad Clínica (EPO En Cirugía) Reducir el número de trasfusiones Menos complicaciones? Mejor pronóstico?

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78 EPO en Cirugía: Dilema Hay incertidumbre sobre la seguridad No hay impacto sobre la supervivencia Coste/efectividad? Depende de nuestro objetivo: Reducir la Necesidad de transfusión: Seleccionar a los pacientes Reducir la Morbi-mortalidad?

79 El empleo de EPO disminuye la necesidad de trasfusión alogénica en pacientes moderadamente anémicos? Grade of Recommendation Clarity of risk/benefit Quality of supporting evidence Implications 1A: Strong Benefits clearly RCTs without important recommendation, outweigh risk limitations or high-quality evidence and burdens, oroverwhelming evidence vice versa from observational studies Strong recommendations, can apply to most patients in most circumstances without reservation 1B: Strong recommendation, moderate-quality evidence Strong recommendations, can apply to most patients in most circumstances without reservation? Benefits clearly RCTs with important outweigh risk limitations (inconsistent and burdens, orresults, methodological vice versa flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies 1C: Strong Benefits clearly Observational studies orstrong recommendation recommendation, outweigh risk case series but may change when low-quality or very low- and burdens, or higher quality evidence quality evidence vice versa becomes available

80 El empleo preoperatorio de EPO mejora el pronóstico de pacientes quirúrgicos? Grade of Recommendation Clarity of risk/benefit Quality of supporting evidence Implications 2A: Weak recommendation, high-quality evidence Benefits closely balanced RCTs without important Weak recommendation, with risks and burden limitations or best action may differ overwhelming evidence depending on from observational studies circumstances or patients or societal values 2B: Weak recommendation, moderate-quality evidence Benefits closely balanced RCTs with important with risks and burden limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies Weak recommendation, best action may differ depending on circumstances or patients or societal values 2C: Weak recommendation, Low-quality or very low-quality evidence Uncertainty in the Observational studies or estimates of benefits, case series risks, and burden; benefits, risk, and burden may be closely balanced Very weak recommendation; other alternatives may be equally reasonable

81 Empleo de EPO en cirugía: Se puede pero, se debe?

82 Vincent et al, Anesthesiology 2008

83 Vincent et al, Anesthesiology 2008

84 EPO Estudios: EPO frente a Control: Reducción de trasfusiones EPO frente a donación autóloga: +/ EPO + Donación autóloga frente a Donación autóloga sola: +/-

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86 EPO: Consideraciones Fisiológicas Qué hace que se libere EPO? Qué inhibe la liberación de EPO? Cómo actúa la EPO Cuando está indicada la EPO? Qué nivel de Hb es el adecuado? Cuales son los riesgos?

87 Elección del endpoint EPO: Reduce el riesgo de necesitar transfusión Reducir morbi-mortalidad? Reducir costes?

88 J Orthop Surg (Hong Kong) Dec;17(3): Combined preoperative autologous blood donation and intra-operative cell salvage for hip surgery. Kubota R, Nozawa M, Matsuda K, Maezawa K, Kim SG, Maeda K, Ikegami T, Hayashi K, Nagayama M, Kaneko H. Department of Orthopaedic Surgery, Juntendo University Nerima Hospital, Tokyo, Japan. PURPOSE: To review records of 161 consecutive hip surgery patients for whom preoperative autologous blood donation (PABD) was used in combination with intra-operative cell salvage (ICS). METHODS: 114 women and 14 men aged 41 to 86 (mean, 64) years underwent 135 primary total hip arthroplasties (THAs), whereas 19 women and 7 men aged 16 to 52 (mean, 35) years underwent 26 rotational acetabular osteotomies (RAOs). Two or 3 weeks before the operation, patients deposited one unit (400 ml) of blood weekly, so long as their haemoglobin levels exceeded 110 g/l (if they had osteoarthritis) or 100 g/l (if they had rheumatoid arthritis). Patients were given oral ferrous sulphate, lactated Ringer's solution, and recombinant human erythropoietin. 800 and 1200 ml of blood were deposited for patients undergoing THA and RAO, respectively. Intra-operatively, ICS was carried out using a continuous autotransfusion system. The blood from ICS was transfused first, and then the blood from PABD was transfused during the latter half of the operation. RESULTS: By combining PABD and ICS, homologous blood transfusion was avoided in all patients, even in those with unexpected massive bleeding during surgery. In 3 patients, one unit of deposited autologous blood was discarded, because they showed no sign of anaemia. The mean total blood loss was almost 1.5 times higher in RAO than in THA patients (1095 vs 1550 ml). In the THA and RAO patients respectively, the mean amount of ICS was 181 and 210 ml, whereas the mean total blood transfusion volume was 975 and 1394 ml. No complications (including infection) related to autologous blood transfusion were observed during PABD, the surgery or the postoperative period. CONCLUSION: Homologous blood transfusion was avoided with the use of PABD and ICS. Preoperative donation of 800 and 1200 ml of blood (combined with ICS) seemed optimal, as only 3 units of blood were discarded. No Complicaciones relacionadas con autologous blood trasfusion.

89 Riesgos: Anemia y Trasfusión ANEMIA Incremento de morbimortalidad (Carson JL et al Transfusión 2002) Isquemia cadiaca Carson JL,et al. Lancet 1996;348: Pacientes mayores Hébert PC, et al Am J Respir Crit Care Med 1997; 155: TRANFUSIÓN Transmisión Hepatitis B y C VIH Virus Priones Inmunosupresión Reacción Alérgica Lesión Pulmonar Aguda Peor Pronóstico

90 Necesidad Clínica Anemia Previsible Tratamiento: Trasfusión Otros Tratamiento de la anemia previsible (cirugía) Diferenciar Lo que se puede hacer Lo que se debe hacer