Trasplante de hígado sin transfusión de sangre permite que testigo
Transcription
Trasplante de hígado sin transfusión de sangre permite que testigo
Trasplante de hígado sin transfusión de sangre permite que testigo de Jehová reciba el órgano Martes 23 de Noviembre de 2010 Fuente :La Segunda Online Paciente de 54 años fue sometido a intervención quirúrgica sin incorporar sangre ajena a su organismo, lo que está prohibido en su religión, y hoy se recupera en su hogar. Había sido desahuciado. Tres años debieron pasar antes de que Luis Salas Sepúlveda pudiera recibir el órgano que le devolvió la vitalidad a su cuerpo cansado y enfermo. Una cirrosis hepática provocada por una esteatohepatitis no alcohólica diagnosticada hace tres años lo mantenía postrado y sin esperanzas de recuperación. Sólo el reemplazo de su hígado le daría una oportunidad de sobrevida. Así fue como la madrugada de viernes 22 de octubre Luis Salas fue intervenido quirúrgicamente por el equipo médico encabezado por el Dr. Juan Carlos Díaz, cirujano jefe de la Unidad de Trasplantes del Hospital Clínico Universidad de Chile, e integrado también por el Dr. Jaime Castillo y el Dr. Gonzalo Cardemil, jefe del Programa de Cirugía sin Transfusión de Sangre del HCUCH, un programa pionero que ha permitido a pacientes Testigos de Jehová acceder a medicina de excelencia, con total respeto a sus creencias. Este es el segundo caso de trasplante hepático realizado mediante prescindencia de sangre en el país, una proeza de la medicina moderna, si se considera que en Chillán, su ciudad de origen, Luis Salas había sido desahuciado. “Vimos a todos los gastroenterólogos de allá y ninguno nos dio esperanzas de vida. Llegábamos llorando a la casa después de ver a los médicos, hasta que un día mi jefe en la empresa donde trabajo me dijo: ‘tú te vas a Santiago para que te mejores’”. Producto de la cirrosis el hígado queda dañado para siempre, forma cicatrices y deja de funcionar correctamente. “Era como un higo seco, como una hoja seca”, recuerda Luis. Hoy disfruta de la vitalidad que un donante anónimo le entregó. A él y a Jehová le agradece, como también al equipo médico del Hospital Clínico Universidad de Chile que respetó su opción y su creencia. “Estoy muy agradecido del doctor Juan Carlos Díaz, que fue como un padre; al Dr. Cardemil, que confió plenamente en mi y que me derivó al Dr. (Danny) Oksenberg, un hepatólogo de excepción, que me cuidó y que me mantuvo estos tres años hasta la operación”, dice al recordar el tránsito desde su anterior estado de postración a esta nueva etapa en su vida. “Hoy siento que Jehová me ha dado una nueva oportunidad, para servir más plenamente y mejor a mi familia y a los demás. Tengo nuevas metas espirituales, deseos de establecerme en Santiago y volver a trabajar en la empresa que me ayudó a estar aquí”, explica, mientras se prepara para tocar su armónica nuevamente, algo que hace unos días era impensado. Martes 23 de Noviembre de 2010 Fuente :La Segunda Online Paciente de 54 años fue sometido a intervención quirúrgica sin incorporar sangre ajena a su organismo, lo que está prohibido en su religión, y hoy se recupera en su hogar. Había sido desahuciado. Tres años debieron pasar antes de que Luis Salas Sepúlveda pudiera recibir el órgano que le devolvió la vitalidad a su cuerpo cansado y enfermo. Una cirrosis hepática provocada por una esteatohepatitis no alcohólica diagnosticada hace tres años lo mantenía postrado y sin esperanzas de recuperación. Sólo el reemplazo de su hígado le daría una oportunidad de sobrevida. Así fue como la madrugada de viernes 22 de octubre Luis Salas fue intervenido quirúrgicamente por el equipo médico encabezado por el Dr. Juan Carlos Díaz, cirujano jefe de la Unidad de Trasplantes del Hospital Clínico Universidad de Chile, e integrado también por el Dr. Jaime Castillo y el Dr. Gonzalo Cardemil, jefe del Programa de Cirugía sin Transfusión de Sangre del HCUCH, un programa pionero que ha permitido a pacientes Testigos de Jehová acceder a medicina de excelencia, con total respeto a sus creencias. Este es el segundo caso de trasplante hepático realizado mediante prescindencia de sangre en el país, una proeza de la medicina moderna, si se considera que en Chillán, su ciudad de origen, Luis Salas había sido desahuciado. “Vimos a todos los gastroenterólogos de allá y ninguno nos dio esperanzas de vida. Llegábamos llorando a la casa después de ver a los médicos, hasta que un día mi jefe en la empresa donde trabajo me dijo: ‘tú te vas a Santiago para que te mejores’”. Producto de la cirrosis el hígado queda dañado para siempre, forma cicatrices y deja de funcionar correctamente. “Era como un higo seco, como una hoja seca”, recuerda Luis. Hoy disfruta de la vitalidad que un donante anónimo le entregó. A él y a Jehová le agradece, como también al equipo médico del Hospital Clínico Universidad de Chile que respetó su opción y su creencia. “Estoy muy agradecido del doctor Juan Carlos Díaz, que fue como un padre; al Dr. Cardemil, que confió plenamente en mi y que me derivó al Dr. (Danny) Oksenberg, un hepatólogo de excepción, que me cuidó y que me mantuvo estos tres años hasta la operación”, dice al recordar el tránsito desde su anterior estado de postración a esta nueva etapa en su vida. “Hoy siento que Jehová me ha dado una nueva oportunidad, para servir más plenamente y mejor a mi familia y a los demás. Tengo nuevas metas espirituales, deseos de establecerme en Santiago y volver a trabajar en la empresa que me ayudó a estar aquí”, explica, mientras se prepara para tocar su armónica nuevamente, algo que hace unos días era impensado. Documento descargado de http://www.revespcardiol.org el 18/08/2010. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. 17C Breves 7055-507-509 5/5/06 13:21 Página 507 COMUNICACIÓN BREVE Cirugía cardiaca en testigos de Jehová. Experiencia en Santander José M. Bernal, Sara Naranjo, Manuel Trugeda, Aurelio Sarralde, Carmen Diago y José M. Revuelta Cirugía Cardiovascular. Hospital Universitario Marqués de Valdecilla. Universidad de Cantabria. Santander. España. Los testigos de Jehová constituyen una población de difícil tratamiento para las intervenciones de cirugía cardiaca. Entre 1998 y 2004, todos los pacientes testigos de Jehová con indicación de cirugía cardiaca (n = 10) fueron intervenidos por un mismo equipo. El descenso medio del hematocrito fue, durante la circulación extracorpórea, del 30%, durante el postoperatorio, del 35% y en el alta, del 22%. Un paciente precisó una reintervención precoz por sangrado importante de origen esternal. Todos los pacientes fueron dados de alta y durante el seguimiento un enfermo falleció de causa respiratoria. Las medidas para disminuir y recuperar la pérdida de sangre permiten realizar intervenciones de riesgo hemorrágico en pacientes testigos de Jehová. Palabras clave: Cirugía cardiaca. Cirugía sin transfusión. testigos de Jehová. Cardiac Surgery in Jehovah’s Witnesses. Experience in Santander, Spain As patients who are Jehovah’s Witnesses are against blood transfusion, they are difficult to manage when a cardiac intervention is required. Between 1998 and 2004, all Jehovah’s Witness patients with an indication for cardiac surgery (n=10) were operated on by the same multidisciplinary team. The mean fall in hematocrit was 30% during cardiopulmonary bypass, 35% during the postoperative period, and 22% at discharge. One patient required cardiac re-exploration because of sternal bleeding. All patients survived operation and were discharged. At follow-up, 1 patient died due to respiratory failure. Technological developments that reduce bleeding and enable lost blood to be recovered have made it possible to perform operations involving a risk of hemorrhage in Jehovah’s Witnesses. Key words: Cardiac surgery. Bloodless surgery. Jehovah’s Witnesses. Full English text available from: www.revespcardiol.org INTRODUCCIÓN Los testigos de Jehová suponen un desafío para la medicina en general y para la cirugía en particular. Sus fuertes convicciones religiosas y su forma de interpretar ciertos pasajes bíblicos (Génesis 9: 2-4, Hechos de los Apóstoles 15: 28,29) les lleva a rechazar, por prohibición divina, cualquier tipo de transfusión. La población de testigos de Jehová en España es de 125.000, de los cuales 1.000 viven en Cantabria. El desafío se produce por el choque entre 2 conciencias: la deontológica del médico que lucha para preservar la vida en grave peligro y la religiosa del paciente. Recientemente, se han instaurado programas quirúrgicos mayores denominados cirugía sin sangre. Estos programas, además del enorme beneficio que representa para los pacientes y para la sociedad, permiten ofrecer al testigo de Jehová la posibilidad de intervención, respetando sus convicciones, con unos riesgos disminuidos. MÉTODOS Correspondencia: Dr. J.M. Bernal. Cirugía Cardiovascular. Hospital Universitario Marqués de Valdecilla. Avda. Marqués de Valdecilla, s/n. 39008 Santander. España. Correo electrónico: [email protected] Recibido el 21 de marzo de 2005. Aceptado para su publicación el 18 de octubre de 2005. Entre 1998 y 2004, 10 pacientes testigos de Jehová fueron intervenidos de cirugía cardiaca en nuestro centro. En este tiempo, ningún paciente fue rechazado por su negativa a recibir transfusiones de sangre. Por una parte, los pacientes firmaron un consentimiento informado elaborado por el comité deontológico del hospiRev Esp Cardiol. 2006;59(5):507-9 507 ABREVIATURAS ARA II: antagonistas de l de la angiotensina II. EC: enfermedad coronari DM: diabetes mellitus. HTA: hipertensión arteria IAM: infarto agudo de m IECA: inhibidores del en de la angiotensina. Documento descargado de http://www.revespcardiol.org el 18/08/2010. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. 17C Breves 7055-507-509 5/5/06 13:21 Página 508 Bernal JM et al. Cirugía cardiaca en testigos de Jehová tal que incluía una aclaración sobre su condición religiosa, su negativa a las transfusiones de sangre o derivados y su aceptación de las posibles repercusiones que podrían producirse, incluso el riesgo de perder la vida. Por otra parte, los profesionales que participaron en las mencionadas intervenciones (anestesia, cirugía y cuidados postoperatorios) se comprometieron a respetar la voluntad del paciente. Tanto la anestesia como la intervención quirúrgica y los cuidados intensivos postoperatorios estuvieron a cargo del mismo equipo de profesionales. El grupo está formado por 5 varones y 5 mujeres con una edad media de 59,8 ± 6,5 años. La indicación quirúrgica fue una valvulopatía en 6 pacientes, una enfermedad coronaria en 3 y ambas en uno. Nueve pacientes se encontraban en clase funcional III según la NYHA y uno en clase IV. Tanto el hemograma como los estudios de coagulación estaban en los rangos de la normalidad 24 h antes de la intervención. Todos los pacientes recibieron aprotinina (Traxylol®) en dosis de 500.000 unidades en la inducción anestésica y 1.500.000 unidades en el cebado de la bomba de circulación extracorpórea. Nueve pacientes fueron intervenidos con circulación extracorpórea (CEC) y uno sin CEC. Se realizaron 2 procedimientos de revascularización miocárdica coronaria con CEC y uno sin CEC, un recambio valvular aórtico y doble pontaje coronario en uno, un recambio valvular aórtico en 2, un recambio valvular mitral en 2, recambio valvular mitral y anuloplastia tricúspide en uno y doble recambio valvular mitral y aórtico en uno. RESULTADOS El tiempo medio de bypass cardiopulmonar fue de 94,6 ± 28,1 min y el de isquemia miocárdica de 66,1 ± 20,8 min. El ahorro de sangre se realizó con la disminución de las pérdidas de sangre y la recuperación del máximo posible de sangre perdida. Se realizó una hemostasia exquisita, extremando las medidas habituales. Se emplearon gasas hemostásicas tipo Surgicel® y todas las cardiotomías fueron aseguradas con colas biológicas con Tissucol® administrado en aerosol. Se utilizó el recuperador de células con reinfusión continua Haemonetis®. De los 10 pacientes intervenidos quirúrgicamente, sólo se reinfundió la sangre recuperada en 3 casos (sangre recuperada: 137, 400 y 510 ml). El sangrado registrado a través de los drenajes torácicos fue de 532 ± 239 ml, con un rango entre 200 y 950 ml. Entre las complicaciones postoperatorias inmediatas destaca una reintervención precoz por sangrado postoperatorio de origen esternal y una reintervención tardía por dehiscencia esternal. De los 10 pacientes intervenidos, se indicó suplemento con hierro por vía oral en 6 y suplemento de ácido fólico en uno. El tiempo medio de ingreso hospitalario fue de 13,2 ± 5,4 días. En cuanto a la evolución del hemogra508 Rev Esp Cardiol. 2006;59(5):507-9 TABLA 1. Evolución del hematocrito Pre-IQ Hematocrito, media ± DE (%) Descenso Rango CEC Post-IQ Alta 40,2 ± 4,6 28,1 ± 3,9 26,2 ± 5,2 31,3 ± 3,4 30,1% 34,6% 22,1% 35-46% 18-35% 21-42% 26-39% CEC: circulación extracorpórea; IQ: intervención quirúrgica; Post-IQ: valor más bajo después de la intervención. ma durante toda la estancia hospitalaria, se muestra en la tabla 1. Durante el seguimiento (entre 1 y 6 años; media, 3,3 años) un paciente falleció por insuficiencia respiratoria terminal y un paciente tuvo que ser reoperado a los 8 meses por una pericarditis constrictiva. Los 9 pacientes supervivientes han seguido una evolución favorable. DISCUSIÓN Probablemente sean los testigos de Jehová la comunidad que más ha contribuido a concienciar a los profesionales de la necesidad de ahorrar al máximo las necesidades de sangre en los procedimientos quirúrgicos mayores, como la cirugía cardiaca con circulación extracorpórea. Ya en 1977, el grupo de Cooley1 publicó su experiencia en cirugía cardiaca en testigos de Jehová y mostró que, aunque algunos pacientes fallecían por falta de transfusión, el riesgo global no estaba gravemente elevado. En España, la primera experiencia quirúrgica con pacientes de esta comunidad pertenece a Iglesias et al en 19812. Otro estudio realizado en España evalúa la evolución del hemograma tras la cirugía cardiaca con CEC sin transfusión de sangre y se ha observado que en las intervenciones no complicadas, el descenso máximo del hematocrito es de un 33%, cifra que se obtiene durante la CEC y al cuarto día postoperatorio3. En nuestra experiencia, el valor más bajo de hematocrito se obtuvo durante la CEC en un paciente valvular (18,2%), cuyo valor en el momento del alta era del 26,4%, lo cual significa una disminución del 33%. Otro aspecto que se debe tener en cuenta es el momento hematológico (valor del hemograma) a partir del cual se indica la transfusión y que, sin duda, tiene un componente subjetivo que depende del criterio científico del médico responsable. Por otra parte, la pérdida global de sangre se puede atenuar mediante dos acciones. En primer lugar es necesario evitar o disminuir el sangrado. En cirugía cardiaca con CEC, la introducción de la aprotinina ha ocasionado una muy importante reducción de las pérdidas hemáticas perioperatorias y postoperatorias, al igual que el ácido tranexámico. La preparación preoperatoria incluye la utilización preoperatoria de ácido fólico, hierro y de la eritropoyetina recombinante. El sangrado postoperatorio intratable puede tratarse con Documento descargado de http://www.revespcardiol.org el 18/08/2010. Copia para uso personal, se prohíbe la transmisión de este documento por cualquier medio o formato. 17C Breves 7055-507-509 5/5/06 13:21 Página 509 Bernal JM et al. Cirugía cardiaca en testigos de Jehová la reciente utilización del factor VIIa recombinante, con el cual se han obtenido buenos resultados4. La técnica quirúrgica también influye en el sangrado, ya que las incisiones en el corazón son susceptibles de pérdidas hemáticas. En este sentido, los hemostásicos tópicos y los adhesivos tisulares constituyen excelentes recursos para controlar y minimizar el sangrado por las heridas quirúrgicas. Tecnológicamente también son de gran ayuda para este objetivo los nuevos sistemas de hemostasia quirúrgica que utilizan pulsos de vapor, ultrasonidos (bisturí armónico) o rayo argón. La segunda vía de acción es la recuperación y reutilización de la sangre perdida. En este sentido, los testigos de Jehová sólo admiten la sangre que no ha llegado a estar almacenada, por lo que los recuperadores de células que aspiran la sangre que se pierde, la limpian, la centrifugan y la reperfunden son, sin duda, excelentes aliados. Otra línea de investigación en fase experimental está en los sustitutos sintéticos de la sangre como los perfluorocarbonos, la hemoglobina recombinante o los transportadores de oxígeno. Según datos procedentes de esta comunidad religiosa, la población de testigos de Jehová en España es de 125.000 en el año 2005. Por otra parte, el número de procedimientos quirúrgicos cardiacos con CEC y revascularizaciones miocárdicas sin CEC en España es de 427 intervenciones por millón de habitantes y año. Teniendo en cuenta estas cifras, es previsible que las necesidades de intervenciones cardiacas de la población de testigos de Jehová sea de alrededor de 50 pacientes/año, cifra en absoluto irrelevante. En particular, en nuestra área de referencia, con una población estimada de 500.000 habitantes para Cantabria y 1.000 testigos de Jehová, podemos afirmar que ningún paciente perteneciente a esta comunidad, con indicación quirúrgica de cirugía cardiaca, ha sido rechazado por su negativa a recibir transfusiones de sangre, por lo que aunque esta experiencia de 10 pacientes es pequeña, es representativa de las necesidades quirúrgicas de esta comunidad. En la actualidad, la revascularización miocárdica con el corazón latiendo y la cirugía endoscópica permiten el tratamiento quirúrgico de la enfermedad coronaria con un notable ahorro en la pérdida de sangre que beneficia enormemente a esta compleja población5, y además, el riesgo general y particular es predecible con las escalas de riesgo6,7. Los testigos de Jehová y la cirugía cardiaca mantienen una relación muy intensa de la que probablemente ambos han salido beneficiados8. BIBLIOGRAFÍA 1. Ott DA, Cooley DA. Cardiovascular surgery in Jehovah’s witness. Report of 542 operations without blood transfusion. JAMA. 1977; 238:1256-8. 2. Iglesias A, De la Llana R, Larrea JI, Núñez L, Gil Aguado M. Cirugía cardíaca con circulación extracorpórea en testigos de Jehová. Rev Esp Cardiol. 1981;34:367-70. 3. Arís A, Padró JM, Bonnin JO, Caralps JM. Prediction of hematocrit changes in open-heart surgery without blood transfusion. J Cardiovasc Surg. 1984;25:545-8. 4. Herman GD, Hendriks MD, Joost MAA, van der Maaten MD, Joost de wolf MD, Tjalling W, et al. An effective treatment of severe intractable bleeding after valve repair by one single dose of activated recombinant factor VII. Anesth Analg. 2001;93:287-9. 5. Cuenca JJ, Herrera JM, Rodríguez MA, Campos V, Valle JV, Juffé A. Revascularización arterial completa con ambas arterias mamarias sin circulación extracorpórea. Rev Esp Cardiol. 2000;53:632-41. 6. Álvarez M, Colmenero M, Martín P, Prades I, Moreno E, González-Molina M, et al. ¿Se puede identificar mediante el EuroSCORE a los pacientes con mortalidad mínima en cirugía cardíaca? Rev Esp Cardiol. 2003;56:682-6. 7. Cortina JM. Scores de gravedad y complejidad en cirugía cardíaca. Usos y limitaciones. Rev Esp Cardiol. 2005;58:473-6. 8. Holt RL, Martín TD, Hess PJ, Beaver TM, Klodell CT. Jehovah’s witnesses requiring complex urgent cardiothoracic surgery. Ann Thorac Surg. 2004;78:695-7. Rev Esp Cardiol. 2006;59(5):507-9 509 8 V I DA R E F OR M A - Sábado 7 de Octubre del 2006 Cuentan médicos con más de 30 procedimientos alternativos Aceptan no transfundir a testigos de Jehová d Logran convencer a 2 mil especialistas para practicar ‘cirugías sin sangre’ ASÍ LO DIJO A todos los pacientes los operamos como si fueran testigos de Jehová: procuramos el mínimo sangrado posible, recuperamos la sangre que se llega a perder y usamos medicamentos que ayudan a que el paciente sangre menos”. Georgina Montalvo La sangre resultó ser motivo de coincidencia entre ciencia y religión. Para los médicos es un tejido “único e insustituible” y para los testigos de Jehová, según lo que Dios dijo a Noé, es “especial”. Esto ha servido para que la medicina desarrolle y practique procedimientos quirúrgicos que evitan al máximo la pérdida de sangre, y para que los testigos defiendan su postura de no aceptar ser transfundidos. “El paciente testigo de Jehová busca curarse, cree en la ciencia, pero de los miles de tratamientos que hay es uno el que no quiere, y existen alternativas que hacen prescindible la transfusión”, señala Gamaliel Camarillo, director de Información Pública de la asociación religiosa La Torre del Vigía (testigos de Jehová). “No buscamos entrar en controversia con los médicos, si uno de ellos no acepta atender a un testigo, pedimos que nos dé oportunidad de llevarlo con otro que sí quiera”, comenta Dervis Alfonso Estrada, asesor médico de Servicios de Información sobre Hospitales. Cuando la transfusión es inevitable, los testigos cuentan con una Exoneración médica por anticipado, que establece: “Exonero de responsabilidad a los médicos, anestesiólogos y al hospital y su personal por cualquier daño que resulte de mi negativa a aceptar sangre, a pesar del cuidado competente que en otro sentido se me dé”. Aléjese del cansancio profesional Quien lo padece tiene la sensación de que el trabajo lo está consumiendo como si fuera un papel al que le han prendido fuego, de ahí la denominación en inglés que dan al síndrome de agotamiento profesional: burn out. Se trata de un estado donde las exigencias de la vida profesional provocan estrés intenso, que no desaparece cuando la situación que lo desata termina, sino se acumula, explica Jorge Álvarez, profesor de la Facultad de Psicología de la UNAM. Médicos, profesores, psicólogos, enfermeras, rescatistas y todos los profesionales cuyo trabajo implica atender a otras personas son los más susceptibles de desarrollarlo. “Casi a todas las personas que atienden a damnificados de desastres naturales les afecta porque sienten que su trabajo nunca va a acabar y que lo que hacen no es suficiente para que la situación llegue a la calma”, agrega Álvarez, también especialista en primeros auxilios psicológicos. Sin embargo, directivos y ejecutivos de empresas, corredores de bolsa y contadores, entre otros, que tienen una alta responsabilidad en la toma de decisiones, también están expuestos, agrega Juan Manuel Rocha, autor del artículo Síndrome de Burn Out, ¿El Médico de Urgencias Incansable?, publicado en la Revista Mexicana de Medicina de Urgencias. Staff Jefe de Cirugía de Corazón del Hospital General La Raza ASÍ LO DIJO Los testigos de Jehová han hecho una aportación importante a la ciencia médica por hacer reflexionar al gremio médico de que se debe ahorrar la sangre y no usarla de manera deliberada”. QUÉ LO DESATA Ángel Herrera Gómez David Oziel Jefe de Cirugía del Incan ASÍ LO DIJO Un procedimiento anestésico correcto permite aplicar todos los procedimientos para ahorrar sangre, así es que sí podemos ayudar a los testigos de Jehová respetando su postura religiosa”. Isidro Martínez del Valle Anestesiólogo y profesor de Farmacología Miguel Á. Tovar En 1991, los testigos de Jehová crearon Comités de Enlace con los Hospitales, que se encargan de proveer a los pacientes los datos de especialistas dispuestos a tratar sin sangre y a difundir entre los médicos las opciones que existen para evitar la transfusión, explica Alfonso Estrada. Existen 75 comités con los que trabajan 950 voluntarios en el País, y según Estrada, son alrededor de 2 mil médicos los que están dispuestos a atender a los pacientes sin recurrir a la transfusión si lo requieren. Ángel Herrera Gómez, jefe de Cirugía del Instituto Nacional de Cancerología (Incan); Moisés Calderón Abbo, jefe de Cirugía de Corazón en el Hospital General La Raza, e Isidro Martínez del Valle, anestesiólogo y profesor de Farmacología en la Escuela Nacional de Enfermería y Obstetricia son algunos de los que han aceptado atender a los testigos respetando su postura, y quienes están convencidos de que las técnicas que emplean con ellos debieran utilizarse con todos los pacientes para evitar los riesgos de una transfusión. “Los testigos ni son necios ni son fanáticos, tienen una postura ante la vida”, comenta Herrera Gómez, quien hace más de 15 años formó un equipo de anestesiólogos y cirujanos que practican los procedimientos quirúrgicos sin sangre. “Desde la aparición de esta organización religiosa en mi vida profesional, me interesé por conocer más acerca de los procedimientos sin sangre”, señala Martínez del Valle, quien forma parte del grupo creado por el cirujano del Incan. Para Calderón Abbo practicar cirugías sin sangre ha sido un procedimiento “de rutina”, pues él hizo la especialidad de cirugía del corazón en el Texas Heart Institute, en Houston, donde se realizó la primera cirugía de corazón en el mundo a un paciente testigo de Jehová sin transfundirlo. “Al regresar a México me di cuenta de que aunque el 85 por ciento de las operaciones se hace sin transfundir al paciente, los médicos piden a los testigos que los exoneren de cualquier responsabilidad”, asegura. Esa actitud, coinciden los médicos, debe evitarse ante los avances. “Una transfusión no es un procedimiento inocuo, existe el riesgo de transmitir virus, bacterias y parásitos, o desarrollar alergias que alteran la función renal y pulmonar”, señala. Pero, como en México el procedimiento “de rutina” es la transfusión, poco se recurre a otras técnicas. Las críticas constantes del jefe o los colegas motivan la aparición del “burn out”. Georgina Montalvo Moisés Calderón Abbo LABOR DE CONVENCIMIENTO d Un ambiente donde el desempeño personal está bajo la mirada crítica de otros colegas, no saber cuál va a ser el resultado del trabajo, sobrecarga de tareas y no contar con la infraestructura y las herramientas necesarias para un buen desempeño son factores que hacen latente la aparición del síndrome. El cansancio y el estrés manifestado en malestares corporales (dolor de cabeza, cardiopatías, hipertensión) y pensamientos negativos también influyen en su desarrollo. Pensar reiteradamente “algo malo va a suceder”, no convivir con la familia y amigos, tener miedo de ir al trabajo o enojarse de manera desproporcionada son signos de que el síndrome está acechando, advierte Rocha. La familia del afectado generalmente es la primera en notar que algo no está bien, pero como mecanismo de defensa y negación, el enfermo decide seguir trabajando para ocultar su malestar; entonces, los compañeros de trabajo y las personas a las que atiende son las víctimas de su mal estado de ánimo. APÁGUELO Si cree que está en esta situación, los expertos recomiendan hablar de inmediato con sus familiares o compañeros de trabajo para comunicarles cómo se siente y por qué. Como es un síndrome que se gesta en un largo periodo, la recuperación también puede llevar tiempo porque el reto, después de aceptar que se padece, es aprender a manejar el estrés y definir, en términos reales, qué es lo que espera de su desempeño profesional. En casos extremos, donde se llega a la depresión, será necesario pedir ayuda a algún psicólogo. Asociación Mexicana para la Ayuda Mental en Crisis www.amamecrisis.com.mx LAS ALTERNATIVAS Cirujanos, anestesiólogos y enfermeras que buscan que los pacientes pierdan la mínima cantidad de sangre en el quirófano tienen por lo menos 30 opciones para lograrlo. Según la cirugía, pueden usar instrumentos que, al mismo tiempo, cortan, coagulan y cauterizan vasos sanguíneos; cubrir los órganos sangrantes con una gasa que desprende sustancias capaces de detener la hemorragia o conectar al paciente a un aparato que recupera la sangre perdida, la limpia y se la regresa. Incluso para casos de emergencia, en los que se pierde mucha sangre rápidamente, existen sustancias que sustituyen el volumen sanguíneo perdido para permitir que la sangre que queda optimice sus funciones y no deje de llegar a órganos vitales, como el cerebro y el corazón. Cirujanos de México, Alemania, Bélgica, Estados Unidos, Francia, Inglaterra y Suiza han asegurado la eficacia y seguridad de estas técnicas. Servicios de Información sobre Hospitales para los testigos de Jehová Correo: [email protected] Conoce otros testimonios de médicos a nivel internacional video La Biblia dice Los testigos de Jehová encuentran en la Biblia más de 500 referencias para no aceptar la transfusión. Noé recibió el mensaje de Dios de que la sangre (de hombres o animales) es sagrada. La cita en la que más se basan es del libro Hechos 15:28-29: “Pues ha parecido bien al Espíritu Santo y a nosotros no imponeros otra carga fuera de éstas, que son indispensables: que os abstengáis de las carnes consagradas a los ídolos, de la sangre, de lo estrangulado y de la fornicación (...)”. “Asumimos que la transfusión es como si comiéramos sangre”, señala Gamaliel Camarillo, director de Información Pública. Incluso no aceptan por separado los componentes principales de la sangre: glóbulos rojos o blancos, plaquetas y plasma; respecto a las fracciones que se obtienen de éstos, queda en el testigo la decisión de aceptarlas o no. Para evitar que llegue Además de que el “burn out” es tratable, existen maneras de prevenirlo: d Duerma por lo menos 6 horas al día d No anule su tiempo libre d Tome vacaciones de manera regular d Emplee el humor en el trabajo d Comparta sus sentimientos sobre el trabajo con sus colegas Técnicas de Conservación Sanguínea y Medicina Sin Sangre en UCI Gabriel E. Pedraza, MD Director, Adult Critical Care Service Bronson Methodist Hospital l uso de transfusiones en UCI es objeto de continua controversia. En este trabajo describo nuestra posición, las observaciones y evidencias en que se basa nuestra apreciación sobre las transfusiones. También relataré el caso de algunos pacientes que nos ayudan a conocer más sobre este problema. Se efectuó una secuestrectomía, dejando la paciente laparostomizada. Durante las siguientes cuatro semanas se hicieron cinco desbridamientos pancreáticos adicionales en el pabellón y se transfundieron siete unidades adicionales de glóbulos rojos. Su hemoglobina durante aquel tiempo oscilaba entre 6 y 7 g/dl. Alrededor de 6 semanas después de su hospitalización, pudimos sacarla de la ventilación mecánica. Después de otras 6 semanas, para un total de 12 semanas en la UCI, se le dio de alta ella con una hemoglobina de 7,4 g/dl. Durante todo el período relatado y que se prolongó por 3 meses, fue transfundida con 10 unidades de sangre. Su hemoglobina nunca fue superior a 8 g/dl durante su estadía en la UCI. Durante los últimos años hemos tenido 5 casos de pancreatitis severas con puntajes APACHE muy altos, en el rango de 20-30. Los valores menores de hemoglobina eran de aproximadamente 6,5 g/dl, el rango era de 5,0 - 7,0 g/dl. En el momento del alta, los valores eran similares. El número total de unidades de GRs transfundidos a estos pacientes era: 10 en la primera paciente, 3, 2, y 2 y uno no transfundido pues era Testigo de Jehová. Todos ellos evolucionaron con SDRA. Una mujer de 31 años de edad se presentó con pancreatitis aguda, con antecedentes de ingesta alcohólica. Los exámenes de laboratorio mostraron valores muy anormales de amilasa, lipasa y triglicéridos, su hemoglobina era 18,8 g/dl y su hematocrito 52,4%, reflejando una severa pérdida de volumen. La TAC mostró pancreatitis edematosa difusa, y la paciente fue ingresada en la UCI para observación. Tres días después ella desarrolló delirium, y un SDRA (Síndrome de Distrés Respiratorio Agudo). Requirió oxígeno a 100% con un PEEP de 20 cm. A la semana de evolución su hemoglobina cayó a 8,2 g/dl y su hematocrito a 23,2%, con un nivel de ácido láctico de 1,8. En ese momento comenzamos terapia con eritropoyetina. Continuó con SDRA por unos diez días más. Logramos bajar la concentración de oxígeno a 50% con un PEEP de 16, la hemoglobina siguió bajando hasta 6,8 g/dl con un hematocrito de 19,4%, para caer luego a 6,1 g/dl con un hematocrito de 18,5%. Decidimos transfundirla. Hay personas que preguntan ¿por qué se hace esto? ¿se justifica mantener hemoglobinas tan bajas en una patología agresiva que tiene una mortalidad muy alta? Ninguno de estos pacientes murió durante su estadía en la UCI. Señalaré algunos datos cuantitativos sobre transfusiones en EEUU durante el último año y sobre manejo de anemia en la UCI. Se colectaron 14 millones de unidades de sangre y se transfundieron 12 millones de unidades en más de 3 millones de pacientes. La mayoría de la sangre transfundida se utiliza en el marco perioperatorio. En la UCI más del 50% de los A las dos semanas de evolución la paciente continuaba muy grave. Su presión intra-abdominal había subido a 25 y requirió una exploración quirúrgica. En ese momento su hemoglobina estaba en 6,3 g/dl y su hematocrito en 19%, y se transfundió con 2 unidades de GR. 24 pacientes tienen anemia. Anticipamos escasez de sangre porque la población se está envejeciendo y el número de donaciones va en mengua. Una unidad de sangre puede costar entre US$ 200 y US$ 1.000, probablemente alrededor de US$ 400 por unidad si se incluye todos los gastos asociados. aceptan. Hay reacciones hemolíticas agudas y tardías. Algunos médicos están al tanto de la inmunomodulación. En términos de los efectos inmunológicos con la sangre transfundida, hay una amplia gama de reacciones que ocurren en las células T y los receptores de citokinas. Entre otros, un aumento en su número, modoficaciones en la hemólisis mediada por células, etc. Todos estos son efectos demostrados in vitro y en algunos casos en vivo en pacientes transfundidos. Incidencia de transfusión en la UCI Jeff Groeger1 del Sloan-Kettering demostró en su estudio que todos los días se transfunden aproximadamente al 14% de los pacientes en UCI. Littenberg2 demostró en un estudio de 1995 que en cualquier estadía en UCI había una probabilidad de 50% de recibir una transfusión. El estudio de Corwin3 en 1995 reveló que cualquier paciente que tenía una estadía en UCI de más de una semana tenía una probabilidad de 85% a ser transfundido, a un promedio de 9,5 unidades/paciente, que es un número muy alto. La mayoría de estos pacientes recibían de 2-3 unidades/semana. La flebotomía era responsable de un 49% de las transfusiones. No hubo una indicación clara de transfusión en el 29% de los pacientes y en aproximadamente un tercio de los pacientes no hubo ninguna indicación en absoluto. Un hematocrito bajo de <25% solo contribuyó en un 19% a la indicación de transfusión. La inmunosupresión mediada por leucocitos, o las citokinas de ellos, en sangre alogénica de donantes puede producir algunos efectos potencialmente beneficiosos. Hay un estudio que demuestra que los pacientes receptores de un trasplante renal tienen mejores resultados cuando reciben más sangre. Y hay un estudio que muestra que cuando se transfunde a pacientes con la enfermedad de Crohn, éstos experimentan una leve mejora. Hay datos recientes que muestran un riesgo aumentado de infección. También hay datos que examinan el aumento de perjuicio post-transfusión o fallo de múltiples órganos. Algunos datos presentados por Robert Taylor4 muestran que hay un impacto en la tasa de infecciones nosocomiales en pacientes transfundidos versus los no-transfundidos. También hay un aumento en mortalidad en pacientes transfundidos versus los no-transfundidos. La mayoría de transfusiones en la UCI no se asocian con pérdidas agudas de sangre. Estas ocurren en el pabellón y antes del ingreso en la UCI, aunque sí ocurren algunas hemorragias gastrointestinales. Sin embargo, existe una necesidad transfusional bastante constante de entre 2-4 unidades por semana. Otro efecto adverso “aceptado” es la sobrecarga de volumen, que algunos médicos pasan por alto. Aproximadamente el 10% de los pacientes que reciben transfusiones de sangre experimentarán edema pulmonar, lo que podría ser desastroso para alguien que esté enfermo de gravedad. Hay un síndrome que ha sido descrito, daño pulmonar agudo relacionado con transfusiones, conocido por su sigla en inglés TRALI, que en muchos casos no es diagnosticado. Una paciente con sangrado post-parto en nuestra UCI recibió 4 unidades de sangre. Menos de 6 horas después de recibir la sangre se presentó SDRA y la paciente requirió oxígeno a 100%. Después insertamos un catéter y encontramos que su presión pulmonar era normal. Sospechamos el síndrome TRALI. En aquel momento la mayoría de los doctores creían que la razón que se presentó SDRA, o lo que ellos llamaron edema pulmonar, era que había recibido 4 unidades La paciente del primer caso estuvo en la UCI por aproximadamente 12 semanas. Considerando 3-4 unidades de sangre por semana, esta paciente probablemente habría recibido en la mayoría de las instituciones entre 36 y 48 unidades de sangre. Nosotros la manejamos con 10. Efectos adversos de las transfusiones Todos mencionan las infecciones y efectivamente existe contaminación viral y bacteriana. Las personas están conscientes de estos riesgos y los aceptan, o por lo menos los médicos que indican transfusiones los 25 de sangre, 3 ó 4 litros de cristaloides y 1 litro de coloides. Pero una persona de solo 32 años de edad con un corazón en muy buenas condiciones debería haber tolerado aquella cantidad. Ya que el catéter mostraba que la presión de oclusión de la arteria coronaria era de 15, esto realmente era un caso de daño pulmonar agudo relacionado con la transfusión. mayoría de los pacientes críticamente enfermos con enfermedad cardíaca, con la excepción de pacientes con infarto agudo del miocardio y angina no estable”. Hay dos ensayos recientes que estudian las transfusiones de sangre en la UCI3,6, el ensayo ABC que incluyó más de 3.500 pacientes de la Europa Occidental, y el ensayo CRIT. El estudio Caracterización de Anemia Adquirida en la UCI de Howard Corwin con casi 5.000 pacientes en 213 hospitales encontró que solo el 19% de los hospitales, menos de uno en cinco, tenían un protocolo institucional para las transfusiones. El valor más común de hemoglobina pre-transfusión para pacientes en UCI fue alrededor de 8 g/dl, y el mismo valor para pacientes con enfermedad cardiovascular era alrededor de 10 g/dl. Cuando se interroga a los intensivistas, ellos dicen, “Ya no transfundimos. Dejamos que la hemoglobina baje hasta 7, a veces hasta 6. Nosotros no creemos en las transfusiones.” Pero los datos muestran lo contrario y todavía están transfundiendo a los pacientes con hemoglobinas de 8, 9 ó 10. De modo que es obvio que todavía no hemos cambiado nuestro manejo de transfusiones sanguíneas en la UCI. Razones para transfundir: realidad y mito Existe la impresión generalizada entre los médicos que la anemia complica otras enfermedades. Los nefrólogos estiman que si alguien tiene anemia, la condición de sus riñones se agravará, y los neurólogos que la condición del cerebro del paciente se agravará. Otros, creen que una transfusión mejorará los síntomas y que si el paciente está en la unidad de cuidados intensivos, es porque es enfermo y que sus síntomas mejorarán si se le da sangre. Desde el punto de vista del intensivista, mejorará la entrega de oxígeno, lo cual mejorará el consumo de oxígeno, lo cual mejora la función de los órganos. Estas son las razones por las cuales los médicos creen que las transfusiones de sangre son beneficiosas. El estudio de Hébert5 de 1999 siguió a dos grupos de pacientes, uno con una estrategia liberal de transfusión y el otro con una estrategia restrictiva. Las transfusiones de sangre en el grupo restrictivo fueron 2,6 unidades versus 5,6 en el grupo liberal. El 33% del grupo restrictivo no recibió ninguna transfusión. Todos los resultados favorecían la estrategia restrictiva: menos mortalidad a los 30 días, menos mortalidad hospitalaria, menos mortalidad en UCI, y una tendencia hacia menos fallo de los órganos. Estos resultados apuntan a un cambio mayor del paradigma en la opinión generalizada del necesario beneficio de la sangre para el paciente críticamente enfermo. Según los resultados del ensayo CRIT, la mayoría de los pacientes tenían anemia el segundo día después de ingresar en la UCI. El 44% de los pacientes recibieron una transfusión durante su estadía. El número promedio era de 5 unidades de transfusiones administradas. También en estos casos, la hemoglobina pre-transfusión era de 8,6 y la edad promedio de los glóbulos rojos transfundidos era de 21,3 días. Las cifras nos indican que los pacientes que pasaron más tiempo en la UCI tenían mas transfusiones, los que recibieron más transfusiones estuvieron más tiempo en ventilación mecánica, más tiempo en la UCI y más tiempo en el hospital. Pero pacientes que tuvieron una hemoglobina más baja también estuvieron más tiempo con ventilación mecánica, más tiempo en la UCI y más tiempo en el hospital, lo que también es importante. En un análisis de sub-grupos se demostró que si el paciente era menos grave y tenía menos edad, específicamente si tenía menos que 55 años de edad y un número APACHE 20, una transfusión empeoraba su condición. La mortalidad de pacientes con enfermedad cardíaca era igual en ambos grupos. El análisis indicó que aún en la presencia de enfermedad cardíaca “una estrategia restrictiva de transfusión de glóbulos rojos generalmente parecía segura en la Eficiencia de la sangre homóloga ¿Cuál es el efecto de la sangre almacenada? En el 26 glóbulo rojo de ésta hay niveles bajos de 2,3 DPG, provocando una gran avidez de la Hb por el oxígeno disminuyendo la entrega de éste a las células. Además condiciona un descenso de ATP en los glóbulos rojos, que lleva a una pérdida de lípidos de la membrana, convirtiendo la forma de disco del glóbulo rojo en esfera, lo cual es menos eficiente para el transporte de oxígeno en la microvasculatura. Esto también hace que los glóbulos sean menos flexibles y que sobrevivan menos tiempo. Existen entre 6 y 8 estudios sobre terapia orientada a una meta en términos de transfusiones y entrega de oxígeno. Estos muestran que aumentar el aporte de oxígeno por transfusión no disminuye la tasa de mortalidad, de modo que no hay ventaja en intentar lograr una terapia orientada a esta meta. Gramm y Smith8 en 1996 examinaron la importancia crítica de la administración aislada de glóbulos rojos en pacientes que están críticamente enfermos. Era un estudio prospectivo con 19 pacientes, y salvo la infusión de hemoglobina, toda la terapia era igual. No hubo cambio en la entrega de oxígeno ni en el consumo de oxígeno. Cambió el pulso cardíaco, lo que era de esperar sin embargo, no hubo cambio en el consumo de O2. Paul Marik7 publicó un estudio en 1993 que mostró el efecto de las transfusiones de GR sobre el consumo de oxígeno por el sistema gastrointestinal y el resto del organismo en 23 pacientes con sepsis y ventilación mecánica. No encontró aumento en el consumo sistémico de oxígeno medido por calorimetría indirecta hasta 6 horas post-transfusión. La gasometría mostró que cuando la sangre transfundida era fresca, había una mejora en el pH, con un descenso en el lactato, pero si la sangre tenía unos 14 ó 15 días de almacenada, estos parámetros incluso empeoraban. De modo que a medida que la sangre envejece, empeoran la microcirculación, la entrega y el consumo de oxígeno. En 1993 en Critical Care Med, Lorente y Landin9 examinaron el efecto de transfusiones en el transporte de oxígeno. Hubo 16 pacientes admitidos en UCI con sepsis, hemoglobina <10 g/dl, que fueron randomizados a grupos de Dobutamina y de Glóbulos Rojos. Encontraron un aumento en entrega y consumo de oxígeno en respuesta a la Dobutamina, pero no hubo cambio en VO2 después de una transfusión de sangre. Estudio tras estudio demuestra que no estamos realmente mejorando el consumo de oxígeno con sangre transfundida. Los estudios de los glóbulos rojos almacenados muestran que la coagulación de la sangre disminuye después de 2 semanas de almacenamiento. Las alteraciones en la forma de los GRs comenzaron a manifestarse también en ese momento y continuaron agravándose en el tiempo. De modo que mientras más tiempo se almacena la sangre, menos efectiva será en aportar oxígeno a los tejidos en caso de ser transfundida. Un estudio publicado en el 2000, efectuado en ratas, comparando resucitación con Ringer Lactato vs GR y Ringer Lactato mostró que la presión era un poco más baja en el grupo con Lactato de Ringer que en el grupo que recibió GRs lavados, probablemente por los efectos de coloide de los glóbulos rojos. La entrega de oxígeno también era más bajo en el grupo de Lactato de Ringer que en el grupo de GRs lavados, que es lo que indicarían nuestros cálculos: si el nivel de hemoglobina es más bajo, la entrega de oxígeno también será más baja. Pero lo que es interesante es que el control de laboratorio medido a nivel de diferentes órganos no mostró diferencias entre ellos. En términos de función de órganos, no hubo ninguna diferencia entre el grupo de GRs y el grupo de Lactato de Ringer, lo que significa que el transfundir GRs no mejoró la respuesta inflamatoria ni la función orgánica de estas ratas. Conocemos bien cómo se relaciona el consumo y el transporte de oxígeno, y sabemos que aquel se mantiene por medio de un aumento de la salida cardíaca en la presencia de anemia. Hay una redistribución del flujo de la sangre y hay mayor extracción del oxígeno. Hay algunos cambios en la afinidad por el oxígeno, y hay reclutamiento capilar. Estas son algunas de las compensaciones para la anemia que permiten mantener la eficiencia en la oxigenación. Pero puede ser que la sangre transfundida no pueda entregar el oxígeno del modo normal, especialmente, como hemos visto, con sangre más vieja. Mi segundo informe de caso es de una paciente testigo de Jehová de 67 años de edad con múltiples 27 problemas médicos. Ingresó en otro hospital con dolor abdominal, distensión, fiebre y una hemoglobina de 7,5 g/dl y una hernia estrangulada y perforada. En el postoperatorio la paciente desarrolló shock séptico severo que requirió altas dosis de vasopresores. extrema, empeorando la hipoxia a medida que aumenta la producción local. Cuando transfundimos sangre hay cierto nivel de hemoglobina libre en la sangre almacenada, la cual puede fijarse al óxido nítrico, empeorando potencialmente la micro-circulación. El estudio con microfotografías de un hígado después de sufrir shock causado por endotoxinas nos muestra una destrucción completa de los vasos capilares y pequeñas venas, con pequeños micro-trombos. Es fácil imaginar lo que pasará si el endotelio está muy enfermo y la microvasculatura también y se transfunde sangre con glóbulos rojos menos flexibles. El glóbulo rojo tiene que deformarse para pasar por los vasos capilares. El tamaño promedio del glóbulo rojo es de aproximadamente 7 micrones y el tamaño promedio del vaso capilar es de aproximadamente 3 micrones. De modo que si estamos administrando sangre que consiste de glóbulos rojos poco flexibles, se puede entender por qué en muchas situaciones las personas empeoran cuando reciben transfusiones10. Evolucionó con niveles altos de ac láctico y un pH de 7 y una hemoglobina de 4,8. Se continuó el soporte y dos días después su pH empezó a subir, el lactato a caer con hemoglobina estable. Probablemente la mayoría de los médicos, frente a una situación así, dirían que la razón que ella tenía hiperlactaticemia (mayor de 5,9, probablemente más cerca de 10) era que había una baja entrega de oxígeno. La única manera de mejorar esta hiperlactaticemia es mejorar la entrega de oxígeno, y la manera más fácil de hacer esto es dar sangre. En esta situación demostramos que sin sangre, la paciente mejoró. También, atendimos otra paciente Testigo de Jehová con hemorragia postoperatoria. Presentaba una hemoglobina cercana a 2, acidosis metabólica severa con hiperlactaticemia. Esencialmente se manejó con vasopresores, obviamente no la transfundimos. La mayoría enfrentados a un paciente con un lactato de 7 y una hemoglobina de 2, dirían que la razón que el paciente tiene hiperlactaticemia era la misma que en la paciente anterior y nuevamente se demuestra que un buen manejo es suficiente. Otro estudio realizado por Zallen11 y publicado en Shock comparó plasma fresco con plasma almacenado incubados con glóbulos rojos almacenados en términos de activación de IL-8. Había una tremenda diferencia en la producción de IL-8 cuando se comparaba plasma incubado con glóbulos de 8 días de vida con plasma que contenía glóbulos de 42 días de vida. Parece que el día 14 ó 15 es el punto crítico, lo cual es consecuente con los datos de Marik7 que mostraron que los glóbulos se hicieron un poco más peligrosos después de 14 días de almacenamiento. La sepsis provoca muchos efectos en la microvasculatura y en los glóbulos rojos. Hay una alteración en el flujo/resistencia. Sabemos que se generan citokines (IL-1, TNF, etc.) Los glóbulos rojos endógenos también pueden perder flexibilidad, lo cual lleva a la formación de un “lodo” de agregados de glóbulos rojos/glóbulos blancos en la microvasculatura. Muchos de estos pacientes tendrán DIC con micro-trombos, todo lo cual contribuye a una disminución del flujo microvascular y de la perfusión de los tejidos. Se acepta cada vez más que la sangre es un agente inflamatorio, hay datos que apoyan esto y que es posible que la transfusión de GRs represente un insulto evitable. Si nuestros pacientes ya sufren de inflamación, tienen sepsis y SIRS, una transfusión puede de hecho empeorar las cosas. Esto está avalado por los trabajos en que se incuba plasma con glóbulos rojos jóvenes y viejos observando apoptosis de neutrófilos12. Encontraron que la apoptosis de PMN se demoró con glóbulos más viejos, lo que podría llevar a mayores efectos de inflamación13,14. Sabemos que el óxido nítrico es un potente vasodilator endógeno pero tiene aproximadamente 8.000 veces mayor afinidad por la hemoglobina que lo que ésta tiene por el oxígeno. Se fija a la molécula de hemoglobina y, ya que la hemoglobina libre no puede regular el óxido nítrico, esto resulta en vasoconstricción En un trabajo realizado por Moore15 en 1997 se estudió la transfusión sanguínea como un factor de 28 riesgo para fallo de múltiples órganos después de sufrir lesiones. Hubo 513 pacientes consecutivos con una calificación de severidad de lesión >15. Examinó la relación de transfusión de sangre, otros índices de shock y otros resultados con fallo de múltiples órganos. Lo que encontró era una relación casi directa: mientras más unidades de sangre había recibido el paciente, mayor la incidencia de fallo de múltiples órganos. El número de pacientes era aproximadamente igual en las distintas condiciones, sin embargo, mientras más unidades había recibido el paciente, más alto el número de calificación de la lesión16. En nuestra institución tenemos equipo de minimuestreo con que podemos hacer muchos exámenes con un volumen de muestra muy pequeño. No sacamos 2 ó 3 cc, sino solamente 90-120 microlitros de sangre. Hay ciertos sistemas avanzados disponibles que devuelven el espacio muerto al paciente. Se saca la muestra, y la porción no utilizada se devuelve de manera segura al paciente. Reduzca el número de catéteres. Si usted tiene buen control de su Unidad de Cuidados Intensivos, estos no son problemáticos. Pero hay muchas UCIs en que las enfermeras sacan sangre solamente porque es fácil hacerlo. Además, se deben eliminar las órdenes fijas para exámenes y los exámenes sin orden médica. Nosotros no tenemos un protocolo de órdenes fijos. En muchas UCIs es una práctica común que los residentes escriban órdenes para exámenes de CDC, LT, sedimentos S y H, lactato, gases sanguíneos, revisen el nivel de hemoglobina cada 4 horas. Recibimos a pacientes que han sido transferidos de otras instituciones donde el paciente ha estado internado por 2 ó 3 días, y el paciente ingresa con hemoglobinas que se han tomado cada 2 ó 3 horas. ¿Cuál es la necesidad de aquello? Tenemos que eliminar “órdenes preestablecidas” de exámenes de sangre y limitar la cantidad de exámenes de sangre para todo paciente, no solamente en pacientes Testigos de Jehová. Se puede tolerar la anemia. Y definitivamente se debe utilizar eritropoyetina humana recombinante (rHuEPO). ¿Cuándo transfundimos? Los gatillos “clásicos” de transfusión utilizan o la hemoglobina o el hematocrito y cuando se llega al umbral, transfundimos. La regla “10/30” provino de un estudio realizado en perros, y también apareció en el estudio de Adams y Lundy que se publicó en Surgical, Gynecological and Obstetrics Journal en 1942. Es increíble que en la actualidad todavía hay médicos que siguen la regla “10/30” basada en un artículo publicado por un anestesista en 1942 que decía que esta era la concentración óptima de la hemoglobina para entrar en el pabellón. Hay enormes lagunas en nuestro c o n o c i m i e n t o , q u e e s p e r a m o s m e j o r a r. Normalmente no hay ninguna razón identificable para la transfusión. Pero la mayoría actúa con la premisa “en caso de duda, transfundamos”. Si realmente es necesario medir la hemoglobina, tenemos el Hemocore, que solo necesita una gota de sangre, es mejor hacerlo de esta manera que extraer 3 ó 4 cc de sangre. Los nuevos umbrales de transfusión dependerán de la experiencia del intensivista. He tenido la buena fortuna de poder atender a la comunidad de testigos de Jehová. En atenderlos a ellos he ganado una enorme cantidad de experiencia y conocimiento. Es verdaderamente asombrosa la tolerancia a la anemia. Lo que intentamos hacer es no solo atender a nuestros pacientes testigos de Jehová, sino utilizar nuestra experiencia y conocimiento para tratar a todos nuestros pacientes. Como se podía ver en la presentación del primer caso, tratamos de limitar la cantidad de transfusiones de sangre en pacientes que no son Testigos. Hemos mejorado nuestro entendimiento de la anemia. Nuestros pacientes de UCI raramente sangrarán, por lo cual nuestro rol es minimizar pérdidas y prevenir sangrados como los gastrointestinales. Sabemos que los niveles endógenos de EPO no están apropiadamente elevados en el paciente críticamente enfermo en la UCI. Buenos estudios muestran que hay una respuesta definitivamente pobre a la anemia en el paciente críticamente enfermo. En parte esto se puede deber al aumento en la producción de citokinas (IL-1, TNF), lo cual puede ser responsable por la respuesta disminuida. Además hay un metabolismo y disponibilidad anormales del hierro. La Eritropoyetina es un fármaco muy bueno. Es fácil de administrar. Es segura. Muchos estudios, entre los cuales están los estudios de Corwin17, y otro de San Diego, que muestran que la eritropoyetina es 29 eficaz en elevar los niveles de hemoglobina y en reducir el número de transfusiones de sangre alogénica en la UCI. Requiere una dosificación adecuada y administración de hierro. Todavía faltan muchos datos para determinar cuál es la dosis óptima de EPO. Actualmente, lo que nosotros estamos haciendo es administrar 40.000 UI/semana a cualquier paciente en la UCI con una hemoglobina de 8. Cualquier paciente que tiene una hemoglobina inferior a 8 recibirá, dependiendo de la situación, hasta 20.000 UI/día, especialmente si son testigos de Jehová y su hemoglobina es muy baja. Con todo paciente que ingresa con una enfermedad severa, como por ejemplo pancreatitis necrótica, y de quién se sabe que estará en la UCI por 2 ó 3 semanas, hemos empezado terapia con EPO tempranamente, aunque su hemoglobina esté superior a 10, pues sabemos que en una semana estará en 6 ó 7. Obviamente no hacemos aquello con todos los pacientes, pero sí con los que creemos que van a permanecer en la UCI por un período prolongado18. tienen miedo de utilizarlo. Básicamente lo utilizamos con todos nuestros pacientes porque, como ustedes saben, la ruta enteral posiblemente no sea una buena manera de entregar hierro a un paciente que esté críticamente enfermo, porque posiblemente no sea absorbido. Esencialmente siempre utilizamos hierro parenteral en pacientes que padecen de anemia. Lo más importante en el manejo en la UCI es mantener la perfusión y la euvolemia. No tiene ninguna utilidad tener una hemoglobina de 4,5 si falta volumen. Es mejor que el paciente tenga una hemoglobina de 3 con una buena perfusión. Es conveniente minimizar el consumo de oxígeno, la sedación es muy importante. Rara vez utilizamos un bloqueador neuromuscular. Incidentalmente, creo que la mayoría de las personas que están en la UCI tienen una sedación inadecuada y un deficiente manejo del ventilador en términos de sincronía del paciente-ventilador, de modo que una vez que estén sedados apropiadamente y bien ventilados evolucionan bien. La entrega de oxígeno y la perfusión son claves. La recomendación es minimizar la pérdida iatrogénica de sangre y utilizar EPO. Evite umbrales estándares de transfusión, administre la sangre sobre la base de una unidad a la vez. Considere todas las variables importantes antes de transfundir: nivel de hematocrito, condición, co-morbididad, y evalúe la rapidez y la cantidad de pérdida de sangre. Hay muchas ventajas en la rHuEPO sobre la transfusión. Estimula la producción de la hemoglobina nativa del paciente versus sangre alogénica. Es medicina basada en evidencia. Mejora la entrega de oxígeno. Mejora la microcirculación, porque no se están utilizando glóbulos viejos. No hay inmunomodulación con sus propias células. Se conserva un recurso escaso. No es que nunca transfundimos a un paciente. Pacientes que necesitan transfundirse deben ser transfundidos. Aunque la EPO es algo costosa, las transfusiones de sangre también pueden salir caras, porque hay muchos costos asociados que a menudo no se toman en cuenta como el tiempo de hospitalización y otros similares. De modo que la pregunta es, ¿puede esperar su paciente? Resumen Los riesgos de la sangre alogénica van mucho más allá de la infección. Es un recurso escaso. Es una práctica no bien definida. Es difícil de aplicar y definir normas universalmente aceptadas. Y hay que reevaluar el equilibrio de demanda y suministro de oxígeno. Como se menciona en el New Zealand Journal of Surgery, “una transfusión sanguínea es como un matrimonio. No debe emprenderse con liviandad, imprudencia o frivolidad, ni más frecuentemente de lo que es absolutamente necesario”20. De EPO generalmente utilizamos: 300 unidades/kg (20.000 unidades) por 5 días y entonces según necesidad, o 600 unidades/kg (40.000 unidades) /semana. Y es muy importante administrar hierro, ácido fólico y vitamina C19. En nuestra institución hemos adquirido una vasta experiencia con hierro parenteral. Sé que no se utiliza en muchos hospitales, y que muchos médicos Referencias: Página 52 en sección español 30 Jueves 20 de Agosto de 2009 Enviar Buscar Búsqueda Avanzada… Salta pa_model7 Pertenecen a la religión de los Testigos de Jehová En Salta, 3.700 personas no aceptan transfusión de sangre Firman un documento para impedirla y se basan en razones religiosas fundadas en la Biblia.Hubo casos en centros asistenciales públicos y privados. En algunos, los médicos tuvieron que recurrir a la Justicia. Jueves 20 de Agosto de 2009 Salta Adrián Quiroga El Tribuno TESTIGOS LEONARDO GUERRERO (IZQUIERDA) JUNTO A SERGIO RAPETTI CUENTAN LAS EXPERIENCIAS DE LAS CONGREGACIONES. En la provincia de Salta hay 3.700 Testigos de Jehová, organizados en 44 congregaciones, que no aceptan transfusiones de sangre aunque sus vidas corran peligro. Las razones son religiosas fundadas en la Biblia. El superintendente de una de ellas y coordinador del comité de enlace con los hospitales, Leonardo Julio Guerrero, de 63 años, informó que desde 1996 fueron transfundidos 7 niños en centros asistenciales públicos y privados y que dos fallecieron. "No les colocaron sangre por mala voluntad de los médicos, sino por la gravedad de los casos. Por lo general los profesionales de Salta respetan nuestra decisión, pero lo hacen muchas veces por temor, por urgencia y porque algunos no conocen el uso de las alternativas", destacó Guerrero en una entrevista con El Tribuno. Los Testigos no aceptan transfusiones de sangre completa, glóbulos rojos, blancos, plaquetas o plasma bajo ningún concepto, aunque el personal médico las crea necesarias para salvarles la vida. También se niegan a que les extraigan sangre para almacenarla y transfundirla posteriormente. Lo dejan establecido con la firma de un documento con directivas anticipadas y la designación de un representante para la atención médica que decida por ellos en caso de hallarse incapacitados. BEBE TRATADO CON ALTERNATIVAS NO SANGUÍNEAS Otro recordado caso de hijos de matrimonios que tienen esa religión sucedió el 17 de septiembre de 1998 en el Hospital de Niños de esta ciudad. "En ese momento el pequeño tenía diez meses y sufría una anemia. Sin embargo no recibió sangre porque les entregamos hierro, ácido fólico y eritropoyetina. Le suministraron los fármacos y se recuperó sin inconvenientes", remarcó Guerrero. El superintendente de una de las congregaciones destacó que tienen muy buena relación con los médicos salteños y que mantuvieron charlas y les entregaron documentación y material bibliográfico a 392 que trabajan en establecimientos públicos y privados, con las alternativas para evitar las transfusiones. De ellos 123 trabajan en el hospital San Bernardo. "Nosotros estamos a favor de la vida. Cada miembro de las congregaciones decide por sí mismo. Nadie está obligado ante situaciones extremas. Se trata de su relación con Dios y de obedecer o no el principio bíblico de no comer sangre", dijo Guerrero. En diálogo con este medio y acompañado por Sergio Eduardo Rapetti, de 41 años, quien es un "anciano" de la congregación y miembro de noticias en la provincia de Salta, Guerrero comentó que fue sometido a dos operaciones en clínicas privadas de esta ciudad y que no recibió transfusión de sangre. "Me intervinieron en la próstata y por una hernia y los médicos utilizaron fármacos que les suministramos", recordó. "Las alternativas son seguras, sencillas y eficaces", destacó Guerrero. Por otra parte, Rapetti informó que en esta ciudad hay 25 congregaciones de Testigos de Jehová, que están integradas por 2.000 personas, y que en el interior de la provincia existen 19 conformadas por 1.700 miembros. Expansores Los pacientes Testigos de Jehová aceptan expansores del volumen sanguíneo no hemáticos. Sostienen que lo correcto son las alternativas médicas a la transfusión de sangre que comprenden el uso sistemático de estrategias clínicas adecuadas para el tratamiento de la hemorragia y de la anemia. Las prácticas combinan fármacos, equipos y técnicas médicas y quirúrgicas con el fin de reducir o evitar la pérdida de sangre y acelerar su producción. Las denominan medicina y cirugía sin sangre, o de ahorro de sangre. Los Testigos sostienen que la vida es sagrada, que por ello debe hacerse todo esfuerzo razonable y humano por mantenerla y prolongarla. Notas Relacionadas Los fundamentos de la negativa “Si es necesario, recurrimos a la Justicia” El fallo de una jueza Pertenecen a la religión de los Testigos de Jehová En Salta, 3.700 personas no aceptan transfusión de sangre Firman un documento para impedirla y se basan en razones religiosas fundadas en la Biblia.Hubo casos en centros asistenciales públicos y privados. En algunos, los médicos tuvieron que recurrir a la Justicia. Los fundamentos de la negativa “Si es necesario, recurrimos a la Justicia” El hombre de la operación de corazón participó de una reunión religiosa 15 March 2011 Asombrosa recuperación del Testigo de Jehová. De vuelta al ruedo. Tras su operación, Jorge Antelaf volvió a su fe. Para algunos fue sorprendente. Es que después de ser reoperado del corazón hace dos semanas sin recibir donaciones de sangre, Jorge Antelaf, participó de una asamblea de testigos de Jehová en Puerto Madryn el fin de semana. El caso fue publicado en exclusiva por Jornada y generó repercusión en el ambiente local. El practicante fue intervenido en el Instituto Cardiovascular “Pueblo de Luis” y la operación se extendió por 5 horas. Médicos formados en la Fundación Favaloro fueron quienes realizaron la cirugía. “Es increíble la recuperación que tuvo Jorge,” destacó uno de los allegados a la familia. Antelaf fue operado por primera vez en 1993 en Buenos Aires. En aquella oportunidad los médicos que participaron de aquella intervención le anticiparon que en 20 años debería ingresar al quirófano nuevamente. Y así lo hizo. El testigo de Jehová fue reoperado, pero sin dadores de sangre, ya que su religión no se lo permite. Tras 5 horas en la sala, el hombre salió airoso de una nueva cirugía a corazón abierto. Antelaf, después de una semana de recuperación, volvió a la iglesia. Y en compañía de su esposa Cristina, le rezó a Díos. http://www.diariojornada.com.ar/10817/Pol%C3%ADtica/El_hombre_de_la_operacion _de_corazon_participo_de_una_reunion_religiosa_ Operación a corazón abierto sin dadores de sangre 15 March 2011 Se trata de un paciente que, por cuestiones religiosas, no recibe transfusiones. Fue en febrero pasado. Nunca se había hecho algo similar en la ciudad. La práctica quirúrgica la realizó un equipo de la Fundación Favaloro. Después del quirófano. Antelaf y Cristina, en una sala común, tras cinco horas de una operación compleja. Cuando la ciencia es bien aplicada, se pueden salvar vidas. Y pasó en Trelew. Jorge Antelaf es testigo de Jehová y en su religión están prohibidas las transfusiones de sangre. Pero la tecnología más avanzada terminó superando los principios bíblicos. Es que esa persona pudo operarse del corazón sin recibir dadores y gracias a una pequeña válvula disfruta con su familia de los placeres cotidianos. Antelaf entró al quirófano el 27 de febrero. Un equipo de especialistas, formado en la Fundación Favaloro, lo recibió. Y durante 5 horas el practicante estuvo en las manos de los profesionales, aunque con la fe puesta en Dios. Su familia siguió segundo a segundo la operación y cuando alrededor de las 15.15 uno de los cardiólogos se acercó a ellos y le dijo, “la operación fue un éxito, el paciente está bien”, se fundieron en un abrazo. Es la primera vez que sea realiza esta práctica de corazón abierto sin dadores en Trelew y en un paciente que ya fue operado hace 20 años de lo mismo. Según describió Marcelo Nahin, médico que operó a Antelaf, “fue una operación riesgosa porque esta persona ya fue operada de lo mismo hace 20 años, o sea, se trató de una reoperación”, que implica un doble compromiso. El lugar de emociones fue el centro de cardiovascular “Pueblo de Luis”. “Este caso es una reoperación cardíaca, o sea, no es una cirugía cardíaca de primera vez. Es un hombre que se operó exactamente hace 20 años en el sanatorio Güemes de la Ciudad de Buenos Aires. Aquella vez se le puso una válvula cardíaca mecánica. Esa válvula le duró 20 años”, por eso “hubo necesidad de cambiarla” ya que “empezó a fallar”, explicó Nahin sobre la práctica. En esta línea agregó: “Él tenía una válvula mecánica monodisco, que se dejó de usar, pero hace 20 años era la que estaba en el mercado. La que se puso ahora es bi-disco, porque tiene dos discos, son dos las puertitas que abren” y permiten el flujo de sangre. “Las reoperaciones cardíacas tienen mayor complejidad, mayor grado de complicaciones y sangrado que aquellas que se hacen por primera vez. En este caso se dio la particularidad que hicimos la reoperación en un paciente que no puede recibir transfusiones de sangre porque es testigo de Jehová”, explicó el profesional. Y consideró que se trata “del primer testigo de Jehová que operamos en Trelew respecto a cirugía cardíaca. Creemos que es también en la Patagonia”. En este marco, el médico comparó que cuando se trabaja en “un paciente sometido a cirugía por primera vez, pedimos de entre 10 a 12 dadores de sangre. Acá no sólo fue de segunda vez y que sangra muchísimo, sino que los dadores fueron cero”. Con Antelaf, explicó Nahin, “se trajo un recuperador celular, save cell, que sería como guarda de las células que es un aparato que recupera algunos glóbulos rojos del campo quirúrgico y eso se puede volver a transfundir. Se vuelve a utilizar la sangre del paciente”, clarificó. El método Más allá de que no hubo transfusión de sangre, todo el éxito pasa por el cambio de métodos. Se reemplazaron válvulas. “La válvula monodisco que sacamos produce mucho torbellino en la sangre porque tiene un sólo disco. Y produce el crecimiento del tejido Pannus que fue el que la obstruyó. Las válvulas biliflet, al tener mayor apertura, tienen mejor performance hemodinámica y no genera ese crecimiento del tejido”, detalló el profesional. “La reoperación cardíaca –comentó el médico- tiene mucho mayor riesgo porque después de la primera cirugía el corazón se pega al hueso, y en la segunda hay que abrir el hueso nuevamente con una cierra especial. En la primera cirugía se usa una cierra de corte directo donde en 10 segundo el hueso se abre. Para esta cirugía, como el corazón está pegado a la cara posterior del hueso esternón, se usa una cierra oscilante, que es muy parecida a las que se usan para retirar yesos; pero para que pase esta cierra se tarda más o menos entre 30 o 40 minutos. Supongamos, si la cierra toca el corazón que está pegado debajo del hueso, se termina la cirugía. Por eso hay que ser delicado y detallista”. En cuanto al proceso de recuperación, “las primeras 48 horas son críticas y un alta estándar en la cirugía cardíaca es a los 7 días”, precisó el médico. La operación cuesta aproximadamente 35 mil pesos “sin contar el recuperador de sangre”, comentó Nahin. que tiene un valor aparte. http://www.diariojornada.com.ar/10695/Pol%C3%ADtica/Trelew_operacion_a_corazon _abierto_sin_dadores_de_sangre Los testigos de Jehová y las transfusiones de sangre. Los testigos de Jehová amamos la vida y acudimos a los médicos para cuidar nuestra salud. No creemos en la curación por fe. En el primer siglo, el apóstol cristiano Pablo indicó que los dones sobrenaturales ‘serían eliminados’. (1 Corintios 13:8.). Por lo tanto los Testigos aceptamos todo tratamiento médico disponible para sostener la vida, incluso los que involucran transfusiones de hierro endovenoso, eritropoyetina, etc., entre otros recursos médicos. La postura de los Testigos sobre abstenernos de sangre es básicamente bíblica. Acatamos la decisión clara del concilio cristiano que se celebró en Jerusalén en el primer siglo, a saber, de “abstenerse [...] de sangre, de animales estrangulados y de uniones ilegales. Haréis bien en guardaros de todo eso”. (Hechos 15:29, Nueva Biblia Española [católica].). Los métodos alternativos no sanguíneos ha dado muy buenos resultados a miles de pacientes testigos de Jehová, al grado que muchos médicos en el mundo se suman día tras día en la postura de evitar las transfusiones de sangre. Esta actitud también la aceptan personas que no practican las creencias de los Testigos. Algunos casos tratados con alternativas no sanguíneas en Argentina: Paciente: Marianella, edad 7 años, atendida en Hospital Garraham. Diagnóstico: MALFORMACIONES VASCULARES. Estas malformaciones afectaron diferentes partes de su cuerpo, principalmente el aparato digestivo, donde se producían ampollas sangrantes que la llevaba a constantes estados anémicos. El cuerpo médico hizo consultas con hospitales de España, EE.UU. y México, la respuesta fue que no se había hallado una solución a la patología. A pesar de tal pronóstico, la Jefa de Endoscopía ideó un sistema denominado “por ataduras”, lo que consistía en efectuarle varias operaciones endoscópicas desde la tráquea hasta el cólon. En el tratamiento, se utilizó ácido tranexámico, eritropoyetina hierro sacarato, Se usaron también técnicas como el Recuperador Celular tipo Cell Saber y Hemodilución Normovolemica Aguda. Actualmente Marianella cuenta con 18 años y aún continúa con tratamientos y controles. Paciente: Camila, edad 8 años, Diagnóstico: OPERACIÓN DE CORAZÓN: Cierre de DAP HMD (cateterismo). Fue atendida en Setiembre de 2012 en el Hospital Garraham. La operación se realizó con éxito con estrategias no sanguíneas. Paciente: Jorge, edad 14 años. Diagnostico: TUMOR CEREBRAL (Fibro Angiona de Cabun Nasofaringeo), fue atendido por el equipo de Otorrinolaringología del Hospital Garraham. El equipo médico consideró que se trataba de una operación de alto riesgo, pero se efectuó todo con éxito y sin utilizar sangre. Respecto a los recursos no sanguíneos, El Dr. Jorge Trainini, director del Hospital Presidente Perón de Avellaneda, Bs. As. comentó: “Ante el desafío de no transfundir descubrimos que los pacientes que no transfundíamos estaban mucho mejor. En nuestra especialidad –cirugía cardiovascular- se suele usar mucha sangre, pero nosotros decidimos hacer al revés: no transfundir a ninguno, sea o no testigo de Jehová. Incorporamos mucha tecnología para usar la misma sangre del paciente, al punto que hoy es muy raro que en nuestro servicio se transfunda. Depende de la filosofía con que encare el arte médico y de alejarse de la medicina de mercado”. La Dra. Mabel Maschio, coordinadora del Plan Nacional de Sangre comentó: “Lejos de ser Negativo, el mensaje de los Testigos de Jehová ayudó a realizar importantes protocolos de investigación que permiten disminuir el umbral de transfusiones para todo paciente.” (cita en bastardillas de la revista Viva, negritas nuestras). Algunos ejemplos de técnicas médicas y quirúrgicas sin sangre: Fluidos: Para mantener el volumen sanguíneo y evitar un choque hipovolémico, se usan la solución de lactato de Ringer, el dextrán, el almidón hidroxietílico y otros productos. Algunos fluidos en fase de experimentación transportan oxígeno. Fármacos: Hay proteínas creadas mediante ingeniería genética que estimulan la producción de glóbulos rojos (eritropoyetina), plaquetas (interleuquina 11) y diversos glóbulos blancos (GMCSF, G-CSF). Otros medicamentos reducen significativamente la pérdida de sangre durante las intervenciones quirúrgicas (aprotinina, antifibrinolíticos) o contribuyen a aminorar las hemorragias agudas (desmopresina). Adhesivos biológicos: Se aplican directamente apósitos de colágeno y celulosa para detener las hemorragias. Las colas y selladores de fibrina pueden taponar las punciones o cubrir amplias zonas de tejidos sangrantes. Máquinas de recuperación de sangre: Estas máquinas recuperan la sangre derramada durante una intervención quirúrgica o un trauma, que luego es filtrada y reinfundida al paciente en un circuito cerrado. En casos extremos, pueden recuperarse litros de sangre con este sistema. Técnicas quirúrgicas: La buena planificación, que incluye consultar a especialistas con experiencia, ayuda al equipo quirúrgico a evitar complicaciones. Es vital actuar rápido para detener el sangrado. Las demoras mayores de veinticuatro horas pueden incrementar significativamente la mortalidad. La reducción de las grandes operaciones a varias menores aminora la pérdida total de sangre. Instrumentos quirúrgicos: Algunos cortan y sellan simultáneamente los vasos sanguíneos. Otros sellan la hemorragia en amplias zonas de tejido. Hay instrumentos laparoscópicos o de carácter mínimamente invasivo que permiten operar sin las pérdidas de sangre ocasionadas por las grandes incisiones. En resumen, los Testigos de Jehová nos abstenemos de las transfusiones de sangre en obediencia a un mandato cristiano y bíblico, el cual ya nos referimos arriba, pero, a consecuencia de tal postura esto nos ha ayudado a mantener una buena salud, en vista de los consabidos efectos negativos de las transfusiones sanguíneas. "Albarracini Nieves, Jorge Washinton si medidas precautorias S.C. A. 523, L. XLVIII. s U P l' e m a COI' t e: - 1- La Cámara Nacional de Apelaciones en lo Civil, Sala A, revocó la decisión de la anterior instancia que autorizaba a realizar al Sr. Pablo Albarracini Ottonelli una transfusión de sangre y denegó la medida cautelar solicitada en tal sentido por su progenitor (v. fs. 21/22 y 89/91) Contra dicha decisión, la actora dedujo recurso extraordinario tederal, que fue replicado, denegado en lo relativo a la tacha de arbitrariedad y concedido por la cuestión federal fundada en el artículo 14 de la ley nO 48 (fs. 98/115, 194/213 y 214/215). - IIEntiendo que en este caso se trae a discusión, por un lado, una restricción al derecho a disponer del propio cuerpo y a la libertad religiosa del señor Albarracini Ottonelli, y, por el otro, la preservación de la vida y la salud (v. arts. 14, 19,33 y 75, inciso 22, de la Constitución Nacional y previsiones internacionales concordantes). En tales condiciones existe, sin duda, una cuestión federal en los términos del altículo 14 de la ley nO 48 (Fallos: 319:1363; entre otros). Y sin perjuicio del cauce conferido por la Cámara Civil al recurso, según se detalló supra, lo cierto es que también, y porque en estos términos debería plantearse el debate, V.E. se encuentra habilitada a tratar las cuestiones vinculadas con la alegación de arbitrariedad. -1- -IlI- El artículo II de la ley 26.529, transcripto por la a qua, establece que "Toda persona capaz mayor de edad puede disponer directivas anticipadas sobre su salud, pudiendo consentir o rechazar determinados tratamientos médicos, preventivos o paliativos, y decisiones relativas a su salud. Las directivas deberán ser aceptadas por el médico a cargo, salvo las que impliquen desarrollar prácticas eutanásicas, las que se' tendrán como inexistentes". A fojas 117 obran "las directivas anticipadas" suscriptas por Pablo Albarracini Ottonelli, en donde expresa que es testigo de Jehová y que no acepta transfusiones de sangre completa, glóbulos rojos, glóbulos blancos, plaquetas o plasma bajo ningún concepto, aunque el personal médico las crea necesarias para salvarle la vida. Siendo éste el presupuesto necesario para la aplicación del artículo II citado, la Cámara Civil entendió que otorga plenos efectos jurídicos a pa¡1ir de la sanción de la ley citada y que estas directivas deben ser respetadas dando prioridad a la voluntad del paciente fundada en su derecho a la autodeterminación, sus creencias religiosas y su dignidad, aun cuando en este caso -sostiene el tribunal- las manifestaciones del padre del paciente vuelve relativo este "testamento vital" con base en "su relación oscilante en la práctica de su creencia religiosa". Y agrega en este sentido que no se advierte que haya transcurrido un largo lapso desde que se celebrara este acto -marzo de 2008, conforme fs. 4 y 63 vta.- por lo que no hay ningún elemento que lleve a la alzada a considerar "que pudo haber mediado algún cambio en la idea religiosa del paciente", porque de haber existido intención de modificarlo lo hubiera revocado. -2- "Albarracini Nieves, Jorge Washinton si medidas precautorias S.C. A. 523, L. XLVIII. Sin desconocer que hubo una manifestación expresa y teniendo en cuenta que ésta es fruto de una convicción religiosa, lo cierto es que, en este trance, resultaría relevante oír los pareceres de sus seres queridos. Pero hete aquí que, por un lado, la cónyuge y las personas a quienes el interesado designó como rep~esentantes en esta si- tuación, y por el otro, el padre del paciente, se arrogan la interpretación de la voluntad del nombrado, incapaz de expresarse, trasuntando exigencias contradictorias: unas rechazando la transfusión y otro demandándola. Esta inceltidumbre sobre la voluntad del paciente impide situar el caso en el supuesto del altículo II de la ley 26.529, que la exige como presupuesto básico. Desde otro punto de vista y puesto que no sabemos cuál es actualmente su voluntad ante una situación de vida o muelte como la que está atravesando, resulta " relevante que los médicos intenten salvarle la vida aun por medio de la técnica en debate. Porque más allá de la prohibición religiosa, lo cierto es que se trata de una intervención menor y que de por sí no parece indicar una crueldad terapéutica. Y además, puesto que el Estado asume la responsabilidad de intentar salvar su vida, queda desplazada, en su inconsciencia, su propia responsabilidad ante el credo al que dijo pertenecer. Por lo demás, esta solución se compadece con los protocolos médicos internacionales en la materia y, sobre todo, con lo que establecen las normas superiores. Porque cabe recordar que V.E. ha declarado que el derecho a la vida es el primer derecho de la persona humana, que resulta reconocido y garantizado por la Constitución Nacional, por lo que es de la mayor importancia advertir la especial perspectiva de este derecho (Fallos: 310: 112), pues el primer deber del juez es preservar la vida (Fallos: 324:51, voto del juez Nazareno). -3- y siguiendo la postura adoptada por la jurisprudencia norteamericana, el Estado retiene cuatro intereses fundamentales respecto de las decisiones médicas que deben adoptarse en estas situaciones, a saber: 1) la preservación de la vida; 2) la prevención del suicidio; 3) la protección de terceras personas inocentes; y 4) el mantener la integridad ética de la profesión médica (Satz v. Perlmutter, 362 So. 2d 160, Fla. Dis!. el. App., 1978, entre otros). Pues bien, dentro de la premura ínsita a lo extremo de la situación, es de mi opinión que V.E. puede ordenar la práctica médica tendiente a salvaguardar la vida de Albarracini Ottonelli, en la medida en que el informe médico aún .pendiente, lo indique .como indispensable. Buenos Aires, l° deju!lio de 2012. LUIS SAMJ;I,CO GON1ALEl \'If¡nCfILP¡ A. 523. XLVIII Albarracini Nieves, Jorge washington sI medidas precautorias. Buenos Aires,)- cJ..e JUh{-.D k 2-D-!2.. vistos los autos: "Albarracini Nieves, Jorge Washington si medidas precautorias". Considerando: 1°) nes en lo tancia, Que Civil, denegó la al la revocar rracini el la Cámara Nacional de Apelacio pronunciamiento de primera medida precautoria hington Albarracini los médicos Sala A de Nieves tratantes de Ottonelli a los solicitada por efectos de que se ins Jorge Was autorizase a su hijo mayor de edad Pablo Jorge Alba -internado en la Clínica Bazterrica de esta Ciudad Autónoma de Buenos Aires- a efectuarle una transfusión de sangre que resultaba necesaria para 2°) blo un Jorge Que según Albarracini hematoma surge Ottonelli de una herida de un de robo. En la causa, se tancias tico de reservado, médicos que la citada de 2012). lo pertenece obra una con asisten al Que culto anterioridad a y al lesión arma de- fuego actualidad, en el han dado inguinal como según surge destacado la necesidad "Testigos (conf. corresponde de Jehová", efectuada por él su hospitalización- el lB de de las cons con pronós de informe que con intensiva y señalar y Pa secundario, crítico, terapia estado autos, consecuencia de de su de citado nosocomio área asimismo, declaración constancias encuentra en estado internado transfusión 3°) la las ingresó intraparenquimatoso con motivo intento de su restablecimiento. que en los efectuarle 30 el el mayo paciente expediente marzo de certificada por de 200B escribano piiblico, en la que manifiesta dicha pertenencia y que por tal motivo no acepta transfusiones de sangre. 4°) las Que presentes diciones c6nyuge de habida actuaciones, expresarse de invocando de voluntad y solicitando 5 0) contraban su a el ley 26.529 entendido en impide el dada en giosas su soporte caso el y padre su no se -derecho habia situaci6n en el por que en a la un dejado como la documento que que que expresamente aunque -que los libertad peligrase seglin el medicos- de de se daba se ne su vida. art. 11 de resguardaban autodeterminaci6n, autorreferentes, excepcional ex la citada sin que norma se que eutanasicas. ende, derecho una deconductas derechos paciente sangre de Carnevale, libertad religiosa y de expediente aceptadas supuesto el respetadas su el directivas constitucional For ser de dichas ser las practicas debian el con dicha decisi6n. planteada en en la mencionada expresi6n cuesti6n a iniciarse planteo efectuado por la transfusiones que Eliana los anticipadas" debian como Romina enumerar que de encontraba de relaci6n obrar se opuso al respete seiia16 en "directivas principio diera al sostuvo misma, se momento no autonomia individual, voluntad recibir en alzada generado, Asimismo, la la se despues salud, conciencia-, cuenta de si al la existencia de involucrados vida yala gaba Que que paciente Fablo Albarracini, progenitor habia el por el presada cuenta de a dignidad, llevaban a quo consider6 priorizando la y a la que voluntad autodeterminaci6n, que las tales del sus manifestaciones considerar que pudiese directivas paciente creencias fun reli rea1izadas haber por mediado A. 523. XLVIII Albarracini Nieves, Jorge washington s/ medidas precautorias. one g9'tktkq/_t- _ algUn cambio en la idea religiosa de Pablo, tido intenci6n qUe" hubiese de modificar revocado la el pues de haber exis testamento vital, voluntad expresada en lo el 16gico era instrumento analizado. 6") Que las resoluciones p:t:ecautorias no autorizan el nario cias ya que no definitivas embargo, (Fallos: se refieren a medidas otorgamiento del recurso extraordi principio,el de en 300:1036; earaeter 308:2006, entre senten otros). Sin cabe hacer excepci6n a dicha regla en 'los casos en que, como en autos, o revisten, que lo resuelto cause un agravio que, circunstancias de hecho, pueda ser de tardia, por sumagnitud insuficiente o imposible ieparaci6n ulterior, pues ella acuerda al decis6rio el earaeter de definitivo a los efectos de la apelaci6n'eJttraordi naria del 308:90; art. 14 314:1202 de y la ley 48 323:2790). (conf. Fallos: Asimismo, el rio resulta admisible en la medida queel nado la,inteligencia de ha sida 3" de contraria alderecho la ley 48). 7"; esta Corte publicado te _-. - ',; las en Fallos: afectado por ....• Que remi ten a neg6. a' recibir " clausulas , . ..,,_ .... ,-c yontrarias. a .. profesaba. 316: fundado en 298:409; recurso 300:1036; 8°) examine Que presenta sin perjuicio de particularidades lo que expresado, en alguna el caso medida lo sub dis tinguen del precedente mencionado y que requieren las siguientes precisiones: la Bazterrica festar a primero, en los que estado de médicos tar conforme las a firmó blancos, sonal médico albergar por dudas dado a su notarial de en la el causa de certificación Acta n° cuestionamientos FO eran de que el (conforme De 18 o a acep de marzo aceptar glóbulos aunque el per la vida". del Natalio permitan sena de puno y letra R. de que documento firmado surge no rojos, elementos digitales formulados mani terapias manifestó formal público el concepto existen original 372). clínica pudo las en glóbulos ningún no no dispuesto para salvarme impresiones 372 que estaba cual la validez escribano e el bajo lo a culto. completa, plasma respecto firmas 12, en crea necesarias Que ante procedió los sangre o su que constancia que obra en autos Pablo, tos n° de las hay de por ingresó cuales biológicos documento plaquetas gO) lado, que un "transfusiones o médicos creencias Segundo, 2008, inconsciencia profesionales procedimientos de Pablo Albarracín Strusberg la que certificación Libro de requerimien esta manera quedan despejados en este punto por el actor en el recurso extraordinario. 10) que el Que paciente no al existen momento pruebas de expresar considerado la trascendencia y las tampoco hay para las presiones de considerar terceros o de claras que dicha y convincentes voluntad consecuencias de que la esa voluntad opción no de haya su decisión; fue viciada por efectuada haya sido A. 523. XLVIII Albarracini Nieves, Jorge Washington sl medidas precautorias. g9'<k rkk aak/ l _ / adoptada con otra intenci6n gue Ia de profesar el de, no existen razones para dudar de gue el bl0 ha manifestado su negativa con discernimiento, 11) por posterioridad a abandonado culto mente tipo Ia en de de de menos presumir para gue no contrario, de su mismo monio se realiz6 en el 12) actual Ia diciembre de Ia de esfera Ia de de cual Pa formulado alega documento, regresar 10 a su este gue hijo "y asi podria propio y se generar suficiente Reino de algiin tiempo de como de de Ia para sus demanda, encuentra segUn resulta Sa16n del habria argumento generico y escrito Pabl0 con sucesiva del mantenimiento en el este gue causa, los Testigos dudas sobre aI creen el casado ca actor con una el matri de Jehovâ 2011. dado expresi6n corresponde fue habido una modificaci6n en el credo, recurrente fundamento actualidad Que cini, tiene en mujer de dicho luego hubiese gue 2 transfundido el Sin embargo, reconoce el de respecto Pabl0. en parte oportunidades", precisiones aI otra firma incertidumbre rente cias; Ia distintas decisi6n ser acto por el Por en intenci6n y libertad. Que el a culto. gue de no existen voluntad examinar si realizada esta libertad personal decisi6n gue por se establece Ia validez Pabl0 Albarra encuadra Ia dentro Constituci6n Nacional. 13) rresponde libertad el recordar individual articul0 hombres Que gue 19 de gue ante un gue una en Ia caso de las Ia gue gravedad premisas Constituci6n consagra ningUn modo de "Las ofendan aI del presente fundamentales Nacional acciones orden y a se co de Ia encuentra en privadas Ia moral de los publi- ca, ni perjudiquen a un tercero, exentas de Que, tal Belluscio y Petracchi ha dej ado Fundamental este ca o puede de de su rechos c. otorga de el individuo un ambito de sin citado autonomia las S. al 19, las acciones, hechos y significa gor, el derecho de como se en a la salud la que, la la vida privada sus destinadas familiares a de los la y estan para la 0 fisica difundidas, autorizados para ni (Fallos: sino de ello en y s610 suma, las formas al propio los extraños la a otros areas de habitos En ri esfera aspec las personas violar sin seña16 ambito y, imagen y nadie puede una persona Indalia intimidad. no de econ6mica, cuenta por acer la divulga reservadas divulgaci6n cual violen un fisica Ley Estado individuo, en amistad, ser no situaci6n familiar y de de el del sentimientos, comprende la parte Cor la fundamentales un mental potencial 0 en ilegitima privacidad corporal libertad juridicamente comunidad 0 de perjuicios" teniendo y 19 por y era familiares, datos real circulo integridad daños jueces esta "Ponzetti de Balbin, protege la art. decisiones intimos la personalidad espirituaı vidad no de el si conocimiento un peligro domestica, tos 0 por cuyo dichas resolver que relaciones aceptadas alguna constituida por religiosas, individuo A. " ... creencias vida decisiones caso datos las de tanto en el ciertos individual costumbres, en Asi, art. las interferencia tribunal, de establecido los "Bahamondez", el Atlantida pUlılica la disidencia de citada causa libremente terceros. el la record6 que particulares, 306,1892) que en al adoptar Editorial ci6n como claramente persona, los y la autoridad de los magistrados". 14) te estan s610 reservadas a Dios, tales inmiscuir de su acti su consentimiento y s610 por ley 0 el podrä A. 523. XLVIII Albarracini Nieves, Jorge Waahington sl medidas precautorias. \ justificarse la intromisi6n, rior en resguardo de siempre que medie un interes la libertad de los otros, supe la defensa de sociedad, las buenas costumbres o la persecuci6n del crimen (voto la mayoria, XXXVI "vazquez de V.356. 1aci6n. bre 19 de s/incidente 2003, de Que a todos su disponer ra de validamente oponerse los io a todo limites de les es propio. la base de de su pertenencia, de despliega su cuerpo con tituciona1 (Fallos: que sobre al acciones De la consagra 316:479 16) en este que el presente tales caso, se art. "Bahamondez" Que a o se de voto principios en e1 de vida que de 1a los "e1 art. la cual cuerpo, ordenado la de de con obrar reaccionar por u enervar trata del sefior reconocido declaraci6n que con La estructura sus por el hombre, las cuales y libertad se Constituci6n Dres. de Fayt forman la cons Naciona1" y Barra) . particular encuentran que expresa 1a prerrogativa resultan se segun un bien dada fundamenta de que tentativa la esta traves 19 septiem facultad la caso, por modo, de ape individuo una esfe esta consecuencia, garantizado causa de su propio Ha conlleva En el constitucional libertad. infraestructura en de la Constituci6n Nacional. la norma su vida obrar caci6n de y dicho al y posibilidad esa prerrogativa. como tancial voluntad; prop6sito, 19 atribuir impedimentos propio art. su 30 prerrogativa cuanto su el ha obrar, a tiene se su a la ... " Maqueda). caso una en incidente sentencia de1 Dr. ese sl de de de en actos, sujeta libre citado Evelin Karina hombres sus sobre sefiorio tambien de1 voto de1 los propia vida, 8°; ape1aci6n", tambien de vivencia humana Ferra, de 24 15) concede pueden cons. consid. la apli comprometidos, precisamente, 1as dad espiritua1 e1 creencias re1igiosas, Y es con afirmar que 1a posibi1idad de especifico, 0 de hace cientes a 1a sustento aceptar tienen derecho a hacer opciones a1 idea 1ey 26.529 zar determinadas expresi6n de otorgar 11 sibi1idad de diendo tas 10 que se tendran como en derecho y medico, aun 1as 0 rechazar un tratamiento 2 Que tratamien que acuerdo con 10s pa sus pro e1 por e1 derecho pasarse persona 1egis1ador a aceptar medicos por capaz y decisiones aceptadas a1to mayor anticipadas determinados desarro11ar ser respetada. 0 en 1a recha "con 0 sin esta 1ey e). puede toda ser la Corte sentido capacidad cuando su 11evar10s razones inc. no es posib1e que de sobre su edad por e1 a medico practicas su a po sa1ud, tratamientos re1ativas 1a pu medicos, sa1ud. cargo, eutanasicas, Es sa1 1as que ha re inexistentes. este 1a de procedimientos rechazar imp1iquen 17) si 0 a receptada directivas deberan 1as cordado que aun cuando parezcan irraciona1es paciente 0 pa1iativos, vo sa1ud 0 demas, disponer directivas su (art. reconoce consentir preventivos a1 sido terapias causa" Por art. ha en en e110s y que esa 1ibre e1ecci6n debe Esta su 0 persona1i mencionadas autodeterminaci6n y autonomia persona1; imprudentes, en 1a se1eccionar una forma a1ternativa de pios va10res 0 puntos de vista, o sa1ud, y fisica y 1a integridad corpora1, citado precedente. to 1a para que de Europea "prima decidir rechazo pueda de Derechos facie, si cada acepta causar a una muerte prematura. e1 rechazo son Humanos adu1to 0 no danos Mas raciona1es e1 tratamiento permanentes aun, 0 tiene no a importa irraciona1es, A. 523. XLVIII Albarracini Nieves, Jorge Washington al medidaa precautorias. desconocidas Moscow fusal O aiin and others of de ella tomar en la Que, las que cabe ficada tad, Que, 782 re T. Adult: que Re la adul conciernen en relevante sea que le limitada piiblico individual of (Court of Appeal) . validamente interes In witnesses libertad de una persona circunstancias de que adulta a un conformidad no judicial que tratamiento y no con resultar1a la decisi6n del discernimiento a fundamentales derecho resoluci6n cuando Jehova's aquellos en iinica claramente no a juego forma y de aparecen caso. concluir una persona al la ser algiin interes, 19) dos, puede en el configuradas of referencia cierto, decisiones exista dicho en (Case weekly Law Report por restricci6n tutelar no 3 directamente, casos que v Russia, Treatment, 18) ta inexistentes" los principios constitucionalmente autorizara sanitario a directamente justi someter en contra de individuo hubiera afectara enuncia sido a una su volun dada con ple derechos de terce- ros. As1, moral piiblica, mientras o a los con la a lo pautas Dra. mejor del Highton de Una art. 19 de proteger1a la el a resulten obrar persona derechos cluso piiblicos pertenecen aunque una no ajenos, ofenda sus al orden, comportamientos su privacidad, y hay que molestos terceros colectivo para (Fallos: a 328:2966, la in respetarlos o desentonen disidencia de convertir al No1asco) . conclusi6n Carta fuero Magna contraria en 1ntimo de una la significaria mera f6rmula conciencia o vac1a, aquellas que s610 conductas de tan escasa el mundo importancia exterior que (Fallos: no tuvieran repercusi6n alguna en 316:479, disidencia de los Dres. Be lluscio y Petracchi) . Tal base de sea, tal norma la actos incoacta nan ... n juez segun autos medico de indiquen anterior, que bertad personal informe admisible ello, del en p. la elemental valores personal, de fundados la en que voto al no de lo etica la o la que libre, determi concurrente un del a no existi6 justificara la constancias tratamiento encuadra en algunas mencionadas --conforme que existir recibir religiosas, excepcionales que voluntad cit., negativa concluir la la libertad moderna, la los que 1941). creencias relevante precisamente, realicen Balbinn, precedentemente-- publico Por se consecuencia, sus cabe y exigencia de 19, en circunstancias arrollados teres Que, a es sujeto consid. contrario las rando que conciencia meri tos del desconoce, la base misma de cual nponzetti Petracchi, vista la de creencia 20) en de la dignos (caso de n ... es autonomia convicci6n los punto los en el conside principios en el cas o des algun restricci6n en la in li nombrado. oido del Cuerpo el recurso el senor Medico Procurador Forense, extraordinario -//- se General y decIara interpuesto y se agregado el formalmente confirma el A. 523. XLVIII Albarracini Nieves, Jorge washington sl medidas precautorias. -ff-pronunciamiento la naturaleza de apelado. las Costas cuestiones por SU orden planteadas. en Notifiquese vuelvase. '/ ENRIQUE S PETRACCH\ JUAN CARLOS MAQUEDA VO-I/- atenci6n y a de А. 523. ХLVІІІ Albarracini Nieves, Jorge Washington аl medidas precautorias. -//-ТО DEL SENOR MINISTRO DOCTOR DON CARLOS S. FAYT Considerando: Que remitir а de 10s go, а 10s Fayt ехсерсібп considerando 13 Que persona efectos fundamentos jueces еоп 10s humana у 10 es por asi, porque -re1acionados sefiorio de1 hombre tidad, honor, чuе, еп cuanto pi1b1ica, пі рrоtессібп autoridad su ta1es еп perjudiquen constituciona1 de 10s еоп а caso саЬе 316:479, voto Fa110s sustancia1mente e1 i11timo un derechos su у tanto ana1o parrafo по su vida, sus de1 a1 gozan cuerpo, de 1a la сот su iden trascendentes, orden, а de mas а de dignidad- creencias ofendan 19 у su 11ega -inc1uso(art. esencia1es 1ibertad tercero, чuе magistrados 10s sobre intimidad у еп presente reso1utiva. prenden a1 su e1 de resu1tar manifestado 1a parte e110 reso1ver de1 precedente у Barra, de de 1a 1a amp1ia eximir10s Сопstіtuсібп moral de la Nacio na1) . Por ma1mente e11o, admisib1e sentencia. 1as oido e1 Costas cuestiones el por sefior Procurador Genera1, se recurso se su orden extraordinario еп debatidas. аtепсібп , а у la VO-//- for confirma la naturaleza de oportunamente, vase. cдR1.0S S. FAYr dec1ara devue1- A. 523. XLVIII Albarracini Nieves, Jorge Washington s/ medidas precautorias. -//-TO DEL SENOR MINISTRO DOCTOR DON ENRIQUE SANTIAGO PETRACCHI Considerando: 1 0) ci6n de1 cando 11i, vs SU Sr. Jorge solicita autorice de1 a anticipadas y de g16bu1os para medica", Sr. Pab10 terminos de 10s NO ACEPTO aunque arts. Que de fs. paciente se 4/6, de medico antes citada, encuentra en discernimiento", admitir 1ugar e1 recurso 234 inc. en aque1. "Direc para 1a segiin e1 pUb1ica, manifiesta: de sangre 0 1as "Soy comp1eta, p1asma, crea instancia bajo necesarias (fs. 1a autenticidad de con e1 a y que origina1) . condiciones hizo 232 de C1inica titu1ado p1aquetas 1a decisi6n de primera 1a base 1a invo Ottone representante TRANSFUSIONES (destacado en e1 en sangre Ottone11i persona1 quien, "efectos hijo escribano b1ancos, e1 a documento A1barracini presenta A1barracini mi un 1a Nieves, JOrge de de por con urgente obra un designaci6n 1a vida" mentaci6n de 4/6 g16bu1os concepto, bien parti6 p1eno y rojos, sa1varme fs. Jorge Jehova "no de certificado Pab10 3°) si A1barracini tratantes 10s inician a rea1izar una transfusi6n de a testigo ningiin en se precautoria medicos Que e1 padre medida CABA, CPCC" , atenci6n cua1 de 10s de actuaciones Washington una 2°} tivas 1as condici6n Bazterrica 1° Que de 21/22), 1a docu fundamento de que tomar decisiones 1a medida solicitada por e1 con su padre. 4°} Pab10 na1 de Que ante Jorge A1barracini Ape1aciones en Ottone11i, 10 Civi1, interpuesto 1a Sa1a A de revoc6 1a por 1a 1a esposa de Camara Nacio reso1uci6n de primera instancia, por "primar decisión las el la considerar, directivas principio religiosa... " adoptada por anticipadas, de 5') Que contra Nieves 96/115), fue en raigambre da, la a sultan el jueces mitir salud, a 6') Que la se que debia Ottonelli en encuentran fundadas en libertad de decisión en las y el Sr. conciencia por juego el a quo cuestiones análogas Fallos que a como y Petracchi), a cuyos 502 (fs. 214/215) derecho a eon de la vi examine re conciencia. el debatidas 479, Washington personalisimos el suscita las 316: (fs. "derechos tales Jorge extraordinario recurso libertad religiosa y de "Bahamondez", sub y resueltas (disidencia términos en de los corresponde re en razón de brevedad. ello, traordinario atencién y, esa constitucional", Belluscio Por se cuales concedido están sustancialmente casa Pablo Albarracini interpuso bien que clara cuestiones, 89/92). Albarracini fundamento las otras autodeterminación y de (fs. que entre a y se declara se confirma la naturaleza oportunamente, formalmente de la procedente sentencia. las Costas cuestiones el por debatidas. recurso su orden ex en Notifique devuélvase. ENRIQUE S PETRACCHI ES CaPIA FIEL Poder Judicial de la Nación TEXTO COMPLETO: Suprema Corte: —I— La Cámara Nacional de Apelaciones en lo Civil, Sala A, revocó la decisión de la anterior instancia que autorizaba a realizar al Sr. Pablo Albarracini Ottonelli una transfusión de sangre y denegó la medida cautelar solicitada en tal sentido por su progenitor (v. fs. 21/22 y 89/91) Contra dicha decisión, la actora dedujo recurso extraordinario federal, que fue replicado, denegado en lo relativo a la tacha de arbitrariedad y concedido por la cuestión federal fundada en el artículo 14 de la ley n° 48 (fs. 98/115, 194/213 y 214/215). — II — Entiendo que en este caso se trae a discusión, por un lado, una restricción al derecho a disponer del propio cuerpo y a la libertad religiosa del señor Albarracini Ottonelli, y, por el otro, la preservación de la vida y la salud (v. arts. 14, 19, 33 y 75, inciso 22, de la Constitución Nacional y previsiones internacionales concordantes). En tales condiciones existe, sin duda, una cuestión federal en los términos del artículo 14 de la ley n° 48 (Fallos: 319:1363; entre otros). Y sin perjuicio del cauce conferido por la Cámara Civil al recurso, según se detalló supra, lo cierto es que también, y porque en estos términos debería plantearse el debate, V.E. se encuentra habilitada a tratar las cuestiones vinculadas con la alegación de arbitrariedad. — III — El artículo II de la ley 26.529, transcripto por la a quo, establece que “Toda persona capaz mayor de edad puede disponer directivas anticipadas sobre su salud, pudiendo consentir o rechazar determinados tratamientos médicos, preventivos o paliativos, y decisiones relativas a su salud. Las directivas deberán ser aceptadas por el médico a cargo, salvo las que impliquen desarrollar prácticas eutanásicas, las que se tendrán como inexistentes”. A fojas 117 obran “las directivas anticipadas” suscriptas por Pablo Albarracini Ottonelli, en donde expresa que es testigo de Jehová y que no acepta transfusiones de sangre completa, glóbulos rojos, glóbulos blancos, plaquetas o plasma bajo ningún concepto, aunque el personal médico las crea necesarias para salvarle la vida. Siendo éste el presupuesto necesario para la aplicación del artículo 11 citado, la Cámara Civil entendió que otorga plenos efectos jurídicos a partir de la sanción de la ley citada y que estas directivas deben ser respetadas dando prioridad a la voluntad del paciente fundada en su derecho a la autodeterminación, sus creencias religiosas y su dignidad, aun cuando en este caso —sostiene el tribunal— las manifestaciones del padre del paciente vuelve relativo este “testamento vital” con base en “su relación oscilante en la práctica de su creencia religiosa”. Y agrega en este sentido que no se advierte que haya transcurrido un largo lapso desde que se celebrara este acto —marzo de 2008, conforme fs. 4 y 63 vta.— por lo que no hay ningún elemento que lleve a la alzada a considerar “que pudo haber mediado algún cambio en la idea religiosa del paciente”, porque de haber existido intención de modificarlo lo hubiera revocado. Sin desconocer que hubo una manifestación expresa y teniendo en cuenta que ésta es fruto de una convicción religiosa, lo cierto es que, en este trance, resultaría relevante oír los pareceres de sus seres queridos. Pero hete aquí que, por un lado, la cónyuge y las personas a quienes el interesado designó como representantes en esta situación, y por el otro, el padre del paciente, se arrogan la interpretación de la voluntad del nombrado, incapaz de expresarse, trasuntando exigencias contradictorias: unas rechazando la transfusión y otro demandándola. Esta incertidumbre sobre la voluntad del paciente impide situar el caso en el supuesto del artículo 11 de la ley 26.529, que la exige como presupuesto básico. Desde otro punto de vista y puesto que no sabemos cuál es actualmente su voluntad ante una situación de vida o muerte como la que está atravesando, resulta relevante que los médicos intenten salvarle la vida aun por medio de la técnica en debate. Porque más allá de la prohibición religiosa, lo cierto es que se trata de una intervención menor y que de por sí no parece indicar una crueldad terapéutica. Y además, puesto que el Estado asume la responsabilidad de intentar salvar su vida, queda desplazada, en su inconsciencia, su propia responsabilidad ante el credo al que dijo pertenecer. Por lo demás, esta solución se compadece con los protocolos médicos internacionales en la materia y, sobre todo, con lo que establecen las normas superiores. Porque cabe recordar que V.E. ha declarado que el derecho a la vida es el primer derecho de la persona humana, que resulta reconocido y garantizado por la Constitución Nacional, por lo que es de la mayor importancia advertir la especial perspectiva de este derecho (Fallos: 310:112), pues el primer deber del juez es preservar la vida (Fallos: 324:51, voto del juez Nazareno). Y siguiendo la postura adoptada por la jurisprudencia norteamericana, el Estado retiene cuatro intereses fundamentales respecto de las decisiones médicas que deben adoptarse en estas situaciones, a saber 1) la preservación de la vida; 2) la prevención del suicidio; 3) la protección de terceras personas inocentes; y 4) el mantener la integridad ética de la profesión médica (Satz v. Perlmutter, 362 So. 2d 160, Fla. Dist. Ct. App., 1978, entre otros). Pues bien, dentro de la premura ínsita a lo extremo de la situación, es de mi opinión que V.E. puede ordenar la práctica médica tendiente a salvaguardar la vida de Albarracini Ottonelli, en la medida en que el informe médico aún pendiente, lo indique como indispensable. — Buenos Aires, 1° de junio de 2012. — Luis Santiago González Warcalde. A. 523. XLVIII Albarracini Nieves, Jorge Washington s/medidas precautorias. Buenos Aires, 1° de junio de 2012. Vistos los autos: “Albarracini Nieves, Jorge Washington s/ medidas precautorias”. Considerando: Poder Judicial de la Nación 1°) Que la Sala A de la Cámara Nacional de Apelaciones en lo Civil, al revocar el pronunciamiento de primera instancia, denegó la medida precautoria solicitada por Jorge Washington Albarracini Nieves a los efectos de que se autorizase a los médicos tratantes de su hijo mayor de edad Pablo Jorge Albarracini Ottonelli —internado en la Clínica Bazterrica de esta Ciudad Autónoma de Buenos Aires— a efectuarle una transfusión de sangre que resultaba necesaria para su restablecimiento. 2°) Que según surge de las constancias de autos, Pablo Jorge Albarracini Ottonelli ingresó al citado nosocomio con un hematoma intraparenquimatoso y lesión inguinal secundario, con motivo de una herida de arma de fuego como consecuencia de un intento de robo. En la actualidad, según surge de las constancias de la causa, se encuentra en estado crítico, con pronóstico reservado, internado en el área de terapia intensiva y los médicos que lo asisten han destacado la necesidad de efectuarle la citada transfusión dado su estado (conf. informe 30 de mayo de 2012). 3°) Que asimismo, corresponde señalar que el paciente pertenece al culto “Testigos de Jehová”, y que en el expediente obra una declaración efectuada por él el 18 de marzo de 2008 —con anterioridad a su hospitalización— certificada por escribano público, en la que manifiesta dicha pertenencia y que por tal motivo no acepta transfusiones de sangre. 4°) Que habida cuenta de que al momento de iniciarse las presentes actuaciones, el paciente no se encontraba en condiciones de expresarse por sí misma, Romina Eliana Carnevale, cónyuge de Pablo Albarracini, se opuso al planteo efectuado por el progenitor invocando la existencia de la mencionada expresión de voluntad y solicitando se respete dicha decisión. 5°) Que después de enumerar los derechos que se encontraban involucrados en la cuestión planteada —derecho a la vida y a la salud, autonomía individual, libertad religiosa y de conciencia—, la alzada señaló que el paciente había dejado expresada su voluntad en relación a una situación como la que se había generado, al obrar en el expediente un documento que daba cuenta de “directivas anticipadas” en el que expresamente se negaba a recibir transfusiones de sangre aunque peligrase su vida. Asimismo, sostuvo que dichas directivas —que según el art. 11 de la ley 26.529 debían ser aceptadas por los médicos— resguardaban el principio constitucional de libertad de autodeterminación, entendido como soporte de conductas autorreferentes, sin que se diera en el caso el supuesto excepcional de la citada norma que impide las prácticas eutanásicas. Por ende, el a quo consideró que tales directivas debían ser respetadas priorizando la voluntad del paciente fundada en su derecho a la autodeterminación, sus creencias religiosas y su dignidad, y que las manifestaciones realizadas por su padre no llevaban a considerar que pudiese haber mediado algún cambio en la idea religiosa de Pablo, pues de haber existido intención de modificar el testamento vital, lo lógico era que hubiese revocado la voluntad expresada en el instrumento analizado. 6°) Que las resoluciones que se refieren a medidas precautorias no autorizan el otorgamiento del recurso extraordinario ya que no revisten, en principio, el carácter de sentencias definitivas (Fallos: 300:1036; 308:2006, entre otros). Sin embargo, cabe hacer excepción a dicha regla en los casos en que, como en autos, lo resuelto cause un agravio que, por su magnitud o circunstancias de hecho, pueda ser de tardía, insuficiente o imposible reparación ulterior, pues ello acuerda al decisorio el carácter de definitivo a los efectos de la apelación extraordinaria del art. 14 de la ley 48 (conf. Fallos: 298:409; 300:1036; 308:90; 314:1202 y 323:2790). Asimismo, el recurso extraordinario resulta admisible en la medida que el recurrente ha cuestionado la inteligencia de cláusulas constitucionales y la decisión ha sido contraria al derecho fundado en aquellas (art. 14, inc. 3° de la ley 48). 7°) Que las cuestiones que llegan a conocimiento de esta Corte remiten a aquellas que dieron origen al precedente publicado en Fallos: 316:479 (“Bahamondez”) (LA LEY, 1993D, 130) en el que un paciente afectado por una hemorragia digestiva, con anemia y melena se negó a recibir transfusiones de sangre por considerar que eran contrarias a las creencia del culto “Testigos de Jehová” que profesaba. 8°) Que sin perjuicio de lo expresado, el caso sub examine presenta particularidades que en alguna medida lo distinguen del precedente mencionado y que requieren las siguientes precisiones: primero, que Pablo Albarracini ingresó a la clínica Bazterrica en estado de inconsciencia por lo que no pudo manifestar a los profesionales médicos cuales eran las terapias o procedimientos médicos o biológicos que estaba dispuesto a aceptar conforme a las creencias de su culto. Segundo, que hay constancia de que en el 18 de marzo de 2008, firmó un documento en el cual manifestó no aceptar “transfusiones de sangre completa, glóbulos rojos, glóbulos blancos, plaquetas o plasma bajo ningún concepto aunque el personal médico las crea necesarias para salvarme la vida”. 9°) Que en la causa no existen elementos que permitan albergar dudas respecto de la validez formal del documento señalado, dado que obra en autos el original firmado de puño y letra por Pablo, ante el escribano público N. R. S. que procedió a su certificación (conforme surge de la certificación notarial de firmas e impresiones digitales Libro de requerimientos n° 12, Acta n° 372 F° 372). De esta manera quedan despejados los cuestionamientos formulados en este punto por el actor en el recurso extraordinario. 10) Que no existen pruebas claras y convincentes de que el paciente al momento de expresar dicha voluntad no haya considerado la trascendencia y las consecuencias de su decisión; tampoco las hay para considerar que esa voluntad fue viciada por presiones de terceros o de que la opción efectuada haya sido adoptada con otra intención que la de profesar el culto. Por ende, no existen razones para dudar de que el acto por el cual Pablo ha manifestado su negativa a ser transfundido fue formulado con discernimiento, intención y libertad. 11) Que por otra parte el recurrente alega que con posterioridad a la firma de dicho documento, su hijo habría abandonado el culto para luego regresar a éste “y así sucesivamente en distintas oportunidades”, lo que podría generar algún tipo de incertidumbre respecto del mantenimiento en el tiempo de la decisión de Pablo. Sin embargo, este argumento genérico y carente de precisiones no tiene fundamento suficiente como para al menos presumir que hubiese habido una modificación en sus creencias; al contrario, en el propio escrito de demanda, el actor reconoce que en la actualidad Pablo se encuentra casado con una mujer de su mismo credo, y según resulta de la causa, el matrimonio se realizó en el Salón del Reino de los Testigos de Jehová el 2 de diciembre de 2011. 12) Que dado que no existen dudas sobre la validez actual de la expresión de voluntad realizada por Pablo Albarracini, corresponde examinar si esta decisión se encuadra dentro de la esfera de libertad personal que establece la Constitución Nacional. 13) Que ante un caso de la gravedad del presente corresponde recordar que una de las premisas fundamentales de la libertad individual en la Constitución Nacional se encuentra en el artículo 19 que consagra que “Las acciones privadas de los hombres que de ningún Poder Judicial de la Nación modo ofendan al orden y a la moral pública, ni perjudiquen a un tercero, están sólo reservadas a Dios, y exentas de la autoridad de los magistrados”. 14) Que, tal como recordó la disidencia de los jueces Belluscio y Petracchi en la citada causa “Bahamondez”, esta Corte ha dejado claramente establecido que el art. 19 de la Ley Fundamental otorga al individuo un ámbito de libertad en el cual éste puede adoptar libremente las decisiones fundamentales acerca de su persona, sin interferencia alguna por parte del Estado o de los particulares, en tanto dichas decisiones no violen derechos de terceros. Así, en el caso “Ponzetti de Balbín, Indalia c. Editorial Atlántida S. A. s/daños y perjuicios” (Fallos: 306:1892) (LA LEY, 1986-C, 411) el tribunal, al resolver que era ilegítima la divulgación pública de ciertos datos íntimos de un individuo, señaló que el citado art. 19: “… protege jurídicamente un ámbito de autonomía individual constituida por los sentimientos, hábitos y costumbres, las relaciones familiares, la situación económica, las creencias religiosas, la salud mental y física y, en suma, las acciones, hechos o datos que, teniendo en cuenta las formas de vida aceptadas por la comunidad están reservadas al propio individuo y cuyo conocimiento y divulgación por los extraños significa un peligro real o potencial para la intimidad. En rigor, el derecho a la privacidad comprende no sólo la esfera doméstica, el círculo familiar y de amistad, sino a otros aspectos de la personalidad espiritual o física de las personas tales como la integridad corporal o la imagen y nadie puede inmiscuirse en la vida privada de una persona ni violar áreas de su actividad no destinadas a ser difundidas, sin su consentimiento o el de sus familiares autorizados para ello y sólo por ley podrá justificarse la intromisión, siempre que medie un interés superior en resguardo de la libertad de los otros, la defensa de la sociedad, las buenas costumbres o la persecución del crimen..,” (voto de la mayoría, consid. 8°; también citado en la causa V.356. XXXVI “Vázquez Ferrá, Evelin Karina s/ incidente de apelación. s/incidente de apelación”, sentencia del 30 de septiembre de 2003, cons. 24 del voto del Dr. Maqueda) LA LEY, 2003-F, 437. 15) Que también en ese caso se ha dicho que “el art. 19 concede a todos los hombres una prerrogativa según la cual pueden disponer de sus actos, de su obrar, de su propio cuerpo, de su propia vida, de cuanto les es propio. Ha ordenado la convivencia humana sobre la base de atribuir al individuo una esfera de señorío sujeta a su voluntad; y esta facultad de obrar válidamente libre de impedimentos conlleva la de reaccionar u oponerse a todo propósito, posibilidad o tentativa por enervar los límites de esa prerrogativa. En el caso, se trata del señorío a su propio cuerpo y en consecuencia, de un bien reconocido como de su pertenencia, garantizado por la declaración que contiene el art. 19 de la Constitución Nacional.La estructura sustancial de la norma constitucional está dada por el hombre, que despliega su vida en acciones a través de las cuales se expresa su obrar con libertad. De este modo, vida y libertad forman la infraestructura sobre la que se fundamenta la prerrogativa constitucional que consagra el art. 19 de la Constitución Nacional” (Fallos: 316:479 “Bahamondez” voto de los Dres. Fayt y Barra). 16) Que tales principios resultan de particular aplicación al presente caso, en el que se encuentran comprometidos, precisamente, las creencias religiosas, la salud, la personalidad espiritual y física y la integridad corporal, mencionadas en el citado precedente. Y es con sustento en ellos que es posible afirmar que la posibilidad de aceptar o rechazar un tratamiento especifico, o de seleccionar una forma alternativa de tratamiento hace a la autodeterminación y autonomía personal; que los pacientes tienen derecho a hacer opciones de acuerdo con sus propios valores o puntos de vista, aun cuando parezcan irracionales o imprudentes, y que esa libre elección debe ser respetada. Esta idea ha sido receptada por el legislador en la ley 26.529 al otorgar al paciente el derecho a aceptar o rechazar determinadas terapias o procedimientos médicos “con o sin expresión de causa” (art. 2 inc. e). Por lo demás, no puede pasarse por alto que esta ley en su art. 11 reconoce a toda persona capaz mayor de edad la posibilidad de disponer directivas anticipadas sobre su salud, pudiendo consentir o rechazar determinados tratamientos médicos, preventivos o paliativos, y decisiones relativas a su salud. Estas directivas deberán ser aceptadas por el médico a cargo, salvo las que impliquen desarrollar prácticas eutanásicas, las que se tendrán como inexistentes. 17) Que la Corte Europea de Derechos Humanos ha recordado en este sentido que “prima facie, cada adulto tiene el derecho y la capacidad de decidir si acepta o no tratamiento médico, aun cuando su rechazo pueda causar daños permanentes a su salud o llevarlos a una muerte prematura. Más aun, no importa si las razones para el rechazo son racionales o irracionales, desconocidas o aún inexistentes” (Case of Jehova’s witnesses of Moscow and others v Russia, en referencia a In re T. Adult: Refusal of Treatment, 3 Weekly Law Report 782 (Court of Appeal). 18) Que, por cierto, la libertad de una persona adulta de tomar las decisiones fundamentales que le conciernen a ella directamente, puede ser válidamente limitada en aquellos casos en que exista algún interés público relevante en juego y que la restricción al derecho individual sea la única forma de tutelar dicho interés, circunstancias que claramente no aparecen configuradas en el caso. 19) Que, de conformidad con los principios enunciados, cabe concluir que no resultaría constitucionalmente justificada una resolución judicial que autorizara a someter a una persona adulta a un tratamiento sanitario en contra de su voluntad, cuando la decisión del individuo hubiera sido dada con pleno discernimiento y no afectara directamente derechos de terceros. Así, mientras una persona no ofenda al orden, a la moral pública, o a los derechos ajenos, sus comportamientos incluso públicos pertenecen a su privacidad, y hay que respetarlos aunque a lo mejor resulten molestos para terceros o desentonen con pautas del obrar colectivo (Fallos: 328:2966, disidencia de la Dra. Highton de Nolasco). Una conclusión contraria significaría convertir al art. 19 de la Carta Magna en una mera fórmula vacía, que sólo protegería el fuero íntimo de la conciencia o aquellas conductas de tan escasa importancia que no tuvieran repercusión alguna en el mundo exterior (Fallos: 316:479, disidencia de los Dres. Belluscio y Petracchi). Tal punto de vista desconoce, precisamente, que la base de tal norma “…es la base misma de la libertad moderna, o sea, la autonomía de la conciencia y la voluntad personal, la convicción según la cual es exigencia elemental de la ética que los actos dignos de méritos se realicen fundados en la libre, incoacta creencia del sujeto en los valores que lo determinan…” (caso “Ponzetti de Balbín”, cit., voto concurrente del juez Petracchi, consid. 19, p. 1941). 20) Que, en consecuencia, al no existir constancias en autos que indiquen que la negativa de recibir un tratamiento médico contrario a sus creencias religiosas, encuadra en algunas de las circunstancias excepcionales mencionadas en el considerando anterior, cabe concluir —-conforme a los principios desarrollados precedentemente— que no existió en el caso algún interés público relevante que justificara la restricción en la libertad personal del nombrado. Poder Judicial de la Nación Por ello, oído el señor Procurador General y agregado el informe del Cuerpo Médico Forense, se declara formalmente admisible el recurso extraordinario interpuesto y se confirma el pronunciamiento apelado. Costas por su orden en atención a la naturaleza de las cuestiones planteadas. Notifíquese y devuélvase. — Elena I. Highton de Nolasco. — Carlos S. Fayt (según su voto). — Enrique Santiago Petracchi (según su voto). —Juan Carlos Maqueda. Voto del señor ministro doctor don Carlos S. Fayt. Considerando: Que a los efectos de resolver el presente caso cabe remitir a los fundamentos del precedente de Fallos 316:479, voto de los jueces Fayt y Barra, por resultar sustancialmente análogo, con excepción de lo manifestado en el último párrafo del considerando 13 y la parte resolutiva. Que ello es así, porque los derechos esenciales de la persona humana —relacionados con su libertad y dignidad— comprenden al señorío del hombre sobre su vida, su cuerpo, su identidad, su honor, su intimidad y sus creencias trascendentes, que, en cuanto tales y en tanto no ofendan al orden, a la moral pública, ni perjudiquen a un tercero, gozan de la más amplia protección constitucional que llega —incluso— a eximirlos de la autoridad de los magistrados (art. 19 de la Constitución Nacional). Por ello, oído el señor Procurador General, se declara formalmente admisible el recurso extraordinario y se confirma la sentencia. Costas por su orden en atención a la naturaleza de las cuestiones debatidas. Notifíquese y, oportunamente, devuélvase. — Carlos S. Fayt. Voto del señor ministro doctor don Enrique Santiago Petracchi: Considerando: 1°) Que las actuaciones se inician con la presentación del Sr. Jorge Washington Albarracini Nieves, quien, invocando su condición de padre de Pablo Jorge Albarracini Ottonelli, solicita una medida precautoria urgente a “efectos de que VS autorice a los médicos tratantes de mi hijo en la Clínica Bazterrica de CABA, en los términos de los arts. 232 y 234 inc. 1° del CPCC”, a realizar una transfusión de sangre en aquél. 2°) Que a fs. 4/6 obra un documento titulado “Directivas anticipadas y designación de un representante para la atención médica”, certificado por escribano pública, según el cual el Sr. Pablo Jorge Albarracini Ottonelli manifiesta: “Soy testigo de Jehová y NO ACEPTO TRANSFUSIONES de sangre completa, glóbulos rojos, glóbulos blancos, plaquetas o plasma, bajo ningún concepto, aunque el personal médico las crea necesarias para salvarme la vida” (destacado en el original). 3°) Que la decisión de primera instancia (fs. 21/22), si bien partió de la base de admitir la autenticidad de la documentación de fs. 4/6, antes citada, con el fundamento de que el paciente “no se encuentra en condiciones de tomar decisiones con pleno discernimiento”, hizo lugar a la medida solicitada por su padre. 4°) Que ante el recurso interpuesto por la esposa de Pablo Jorge Albarracini Ottonelli, la Sala A de la Cámara Nacionalde Apelaciones en lo Civil, revocó la resolución de primera instancia, por considerar, entre otras cuestiones, que debía “primar la decisión adoptada por Pablo Albarracini Ottonelli en las directivas anticipadas, las cuales se encuentran fundadas en el principio de autodeterminación y de libertad de conciencia y (fs. 89/92). 5°) Que contra esa decisión el Sr. Jorge Washington Albarracini Nieves interpuso recurso extraordinario (fs. 96/115), que fue bien concedido por el a quo (fs. 214/215) con fundamento en que están en juego “derechos personalísimos de clara raigambre constitucional”, tales como el derecho a la vida, a la salud, a la libertad religiosa y de conciencia. 6°) Que las cuestiones que suscita el sub examine resultan sustancialmente análogas a las debatidas y resueltas en el caso “Bahamondez”, Fallos 316: 479, 502 (disidencia de los jueces Belluscio y Petracchi), a cuyos términos corresponde remitir en razón de brevedad. Por ello, se declara formalmente procedente el recurso extraordinario y se confirma la sentencia. Costas por su orden en atención a la naturaleza de las cuestiones debatidas. Notifíquese y, oportunamente, devuélvase. — Enrique Santiago Petracchi. Original Article European Journal of Trauma and Emergency Surgery Optimizing Outcomes in the Jehovah’s Witness Following Trauma: Special Management Concerns for a Unique Population Chrysanthos Georgiou, Kenji Inaba, Joseph DuBose, Pedro G.R. Teixeira, Pantelis Hadjizacharia, Ali Salim, Carlos Brown, Peter Rhee, Demetrios Demetriades1 Abstract Background: The objective of this study was to describe the management of the Jehovah’s Witness (JW) in an intensely active level I trauma center and review the modern therapeutic options available for the trauma care of these patients. Study design: A retrospective review of injured JWs admitted to a busy trauma center over a 13-year period was conducted. Results: Over the study period, 143 JWs were identified. Among these, 15.4% (22/143) overall and 32.3% (10/31) requiring surgical intensive care unit (SICU) admission accepted transfusion. Overall, 56.6% of JWs (81/143) required operation and 21.7% (31/143) were admitted to the SICU with a complication rate of 4.2% (6/143) and a mortality of 1.4% (2/143). One patient of the 31 patients that were admitted to the SICU received 10 ml of blood with subsequent discontinuation of the transfusion and was excluded from analysis. Of the 30 JWs admitted to the SICU, 20 (66.7%) did not receive transfusion and demonstrated mean admission and nadir hemoglobin (Hb) levels of 12.7 (±2.5) and 9.1 (±3.0) mg/dl, respectively. Ten patients accepted transfusion. This group had longer mean SICU stays (23.3 vs. 5.5 days) but similar mortality (10%, 1/10 vs. 5%, 1/20) compared to non-transfused counterparts. Only one complication (1/20, 5%) was observed in the JWs who were not transfused, compared to a 40% (4/10) complication rate in those accepting transfusion. Conclusion: Although our experience was limited, we found no significant difference in the mortality or morbidity between JW patients who received or 1 abstained from transfusion following major trauma. We should keep in mind that the population was small, in order to extract safe conclusions regarding whether we should transfuse or not transfuse trauma patients. We can, however, see interesting insights on the value of trauma resuscitation. Key Words Injury Æ Wounds and injuries Æ Trauma Æ Outcome assessment Æ Jehovah’s Witnesses Æ Hemoglobin Æ Blood transfusion Eur J Trauma Emerg Surg 2009;35:383–8 DOI 10.1007/s00068-009-8246-6 Introduction There are almost six million Jehovah’s Witnesses (JWs) worldwide, with more than a million residing in the United States [1]. JWs share a belief system that prohibits the receipt of blood or blood products, including whole blood, packed red blood cells, white blood cells, plasma, and platelets. Other components, such as immune globulins, albumin, erythropoietin, and clotting factors, are, however, more commonly considered to be acceptable for use [1]. In the setting of major trauma and hemorrhage, health care providers must reconcile the need to respect the rights of the patient to refuse potentially life-sustaining treatment with their own scientific and ethical desire to do what they have been trained to do – give blood to the symptomatic bleeding patient. Aggressive management approaches and protocols for this special population can serve to minimize Division of Trauma Surgery and Surgical Critical Care, Department of Surgery, USC + LAC Medical Center, University of Southern California, Los Angeles, CA, USA. Received: December 19, 2008; revision accepted: May 8, 2009; Published Online: July 9, 2009 Eur J Trauma Emerg Surg 2009 Æ No. 4 URBAN & VOGEL 383 Review Article The Journal of TRAUMA威 Injury, Infection, and Critical Care The Contemporary Approach to the Care of Jehovah’s Witnesses Duncan B. Hughes, MD, Brant W. Ullery, MD, and Philip S. Barie, MD, MBA, FCCM, FACS Background: Jehovah’s Witnesses are widely known for their prohibition on the acceptance of blood transfusion. Such refusal serves as a potential obstacle to optimal therapeutic intervention among critically injured Jehovah’s Witnesses. As such, care of these patients requires an aggressive and multidisciplinary approach to therapy. Methods: A review of the pertinent English language literature. Results: Jehovah’s Witnesses exercise the right of any adult with capacity to refuse medical treatment and often carry advance directive cards indicating their incontro- vertible refusal of blood. Despite their belief regarding transfusion, Jehovah’s Witnesses do not have a higher mortality rate after traumatic injury or surgery. Transfusion requirements are often overestimated. Increased morbidity and mortality is rarely observed in patients with a hemoglobin concentration >7 g/dL, and the acute hemoglobin threshold for cardiovascular collapse may be as low as 3 g/dL to 5 g/dL. There are many modalities to treat the Jehovah’s Witness patient with acute blood loss. Treatment with recombinant human erythropoietin, albumin, and recombinant activated Factor VIIa have all been used with success. Autologous autotransfusion and isovolemic hemodilution can also be used to treat patients who refuse transfusion. Hemoglobin-based oxygen carriers may play a future role as intravascular volume expanders in lieu of transfusion of red blood cell concentrates. Conclusion: There are many treatment modalities available to assist in the care of Jehovah’s Witness patients, especially since their beliefs on the intricacies of the Blood Ban appear to be in flux. Key Words: Jehovah’s Witness, Transfusion, Trauma, Critical care, Surgery. J Trauma. 2008;65:237–247. J ehovah’s Witnesses trace their origin to a Bible study group founded in Allegheny, PA in 1869 by Charles Taze Russell.1,2 The study group engaged in extensive biblical analysis that led to, in their belief, the detection of fundamental errors in traditional Christian doctrine, including those related to common Christian teachings on the nature of the deity and the immortality of the soul. Indeed, the religious convictions of this following were based on strict literal interpretation of the Bible.1,3,4 Russell and his group members, originally known as Bible Students, believed that disobeying biblical commands would ultimately forfeit any opportunity for eternal life. The study group subsequently rejected much of mainstream Christianity in favor of what they considered to be a restoration of first-century Christianity. A decade later, in 1879, the first issue of an illustrated religious magazine, later called The Watchtower, was published and Russell’s study group sparked the creation of nearly 30 congregations across seven states.2 Initially known as Zion’s Watch Tower Tract Submitted for publication November 17, 2007. Accepted for publication March 24, 2008. Copyright © 2008 by Lippincott Williams & Wilkins From the Department of Surgery (D.B.H., B.W.U., P.S.B.), Division of Critical Care and Trauma, Weill Cornell Medical College, New York, New York; and Department of Public Health (P.S.B.), Division of Medical Ethics, Weill Cornell Medical College, New York, New York. Address for reprints: Philip S. Barie, MD, MBA, Department of Surgery, Weill Cornell Medical College, Payson 713-A, 525 East 68 Street, New York, NY 10065; email: [email protected]. DOI: 10.1097/TA.0b013e318176cc66 Volume 65 • Number 1 Society, the name Jehovah’s Witnesses (based on Isaiah 43: 10 –12) was not adopted until 1931. As the most rapidly growing religious group in the western world, Jehovah’s Witnesses represent an international religious organization comprised of over 6.7 million members worldwide, with more than one million members in the United States.5,6 Members of the organization believe that God’s name is Jehovah and that the use of such is necessary for valid worship.7 Jehovah’s Witnesses are recognized for their person-to-person ministry and for their involvement with literacy programs and disaster relief. To be acknowledged as a member, an individual must be approved as a minister and satisfy a minimum monthly time requirement in the ministry.2 Jehovah’s Witnesses pledge allegiance to God’s Kingdom, an entity that is viewed as an authentic government unto itself, and therefore remain neutral politically.8 Members do not salute flags, join service organizations, enlist in the military, vote in public elections, or take any interest in civil government.9,10 THE BLOOD BAN Because the Watchtower Society, the governing body of Jehovah’s Witnesses, introduced the blood ban in 1945, Jehovah’s Witnesses have been known widely in the medical community for their prohibition on the acceptance of blood transfusion. This position is based on literal interpretation of passages in the Old Testament that allegedly forbid transfusion, namely Genesis 9:3– 4, Leviticus 17:10 –16, and Acts 15:28 –29. For instance, Jehovah’s Witnesses interpret the 237 The Journal of TRAUMA威 Injury, Infection, and Critical Care following passage to mean that God (Jehovah) has forbidden them to “eat blood”: “For it (the blood) is the life of all flesh; the blood of it is for the life thereof; therefore I say unto the children of Israel, ye shall eat the blood of no manner of flesh: for the life of all flesh is the blood thereof. Whoever eateth it shall be cut off” (Leviticus 17:14). In an oft-cited The Watchtower article, receiving blood products intravenously is described to be analogous to literally “eating” blood, or its components therein: “A patient in hospital may be fed through the mouth, through the nose or through the veins. When sugar solutions are given intravenously, it is called intravenous feeding. So the hospital’s own terminology recognizes as feeding the process of putting nutrition into one’s system via the veins. Hence the attendant administering the transfusion is feeding the patient blood through the veins, and the patient receiving it is eating through his veins” (The Watchtower 1951;July:415). The blood ban requires that Jehovah’s Witnesses not accept transfusion of allogeneic blood components, including whole blood, red blood cell (RBCs) concentrates, white blood cells, plasma, and platelets.11–13 Autologous blood must also be refused if predeposited (e.g., preoperative setting). However, autologous blood can be accepted if it is maintained in continuous contact with the patient’s blood (e.g., intraoperative autotransfusion with no disruption or interruption of the tubing circuit). The permissibility of this specific circumstance allows for intraoperative utilization of isovolemic hemodilution and intraoperative RBC salvage as feasible methods to ensure hemodynamic stability, provided that a continuous circuit from the patient to the intravenous tubing and blood bag is maintained.14 Jehovah’s Witnesses who consciously accept a blood transfusion violate the blood ban and were subjected historically to excommunication, or organized communal shunning, under Scriptural doctrine.15 However, the Watchtower Tract Society issued a directive in 2000 stating that the organization would no longer excommunicate members who did not comply with the blood ban.16 The official statement read: “If a baptized member of the faith willfully and without regret accepts blood transfusions, he indicates by his own actions that he no longer wishes to be one of Jehovah’s Witnesses. The individual revokes his own membership by his own actions, rather than the congregation initiating this step.” Issuance of the directive made no change in the end result given that any individual knowingly accepting allogeneic blood products is still considered to be revoking his religious affiliation because he or she no longer accepts and follows a core tenet of the faith. Members of this faith group think generally that blood contains one’s moral and physical characteristics, and that accepting a transfusion will “pollute” oneself with the world’s ideas, thus losing one’s holiness.12 Furthermore, they believe that “the time gained on earth from a blood transfu238 sion is inconsequential to the eternal spiritual damnation that results from it.”15 In fact, the Jehovah’s Witness community will often send a representative from the religion to “stand watch” at the hospital bedside to ensure that no transfusions are administered. There is, however, variability within the religion and not all members approach the Blood Ban equally. For example, many Jehovah’s Witnesses will accept fractions of whole blood, such as albumin, recombinant human erythropoietin (rHuEPO), immunoglobulins, and factor concentrates, whereas others will not. This decision is often left to the individual member.17 If a Jehovah’s Witness patient requests to receive a blood transfusion secretly, it is likely that they will not be discovered by the community, unless they admit the act to a fellow Jehovah’s Witness. As a result, if a Jehovah’s Witness patient privately communicates a desire to receive transfusions, the physician should be reminded that patient confidentiality is of utmost importance, and that confidentiality is vital to avoiding potential social and religious repercussions.17 PHYSICIAN-PATIENT RESPONSIBILITY AND COMMUNICATION When caring for a Jehovah’s Witness patient, available hospital resources are a crucial asset to support the patient’s decision-making process. Many hospitals have an ethics committee available for consultation, and a risk management group available for legal advice. Often at large medical centers with blood conservation programs, there are also transfusion medicine specialists available. In addition, it is possible that a Jehovah’s Witness patient may be confused or unsure of their transfusion options, and may not be aware that certain blood fractions are acceptable to many Jehovah’s Witnesses. There is often a Hospital Liaison Committee of Jehovah’s Witnesses available at major medical centers. This group may address patient questions, and may place inquiring physicians in contact with other physicians with previous experience in similar situations (call 718-560-4300 or e-mail [email protected]).18 Management of the Jehovah’s Witness patient may also pose an ethical dilemma to the supervising physician. In some circumstances, a physician may not think comfortable accepting a Jehovah’s Witness patient given their treatment limitations. There is an emotional burden endured by a health-care provider watching a patient die in a “preventable” medical setting. Physicians should consider these ramifications, and in nonemergent cases, consider transferring the care of a Jehovah’s Witness patient to another health care provider if he or she is encumbered personally.19 Such circumstances would not be considered inappropriate, provided that the transferring physician arranges alternate means of care. Additionally, it is important for the family members to be informed of the reason for the transfer, and that the accepting physicians be made aware of the patient’s medical preferences.18 Whereas Jehovah’s Witnesses frame their objection to blood transfusion on religious grounds, they secure their position by highlighting the hazards associated with such July 2008 Contemporary Approach to Jehovah’s Witnesses medical intervention. The Watchtower Society warns its members that transfusions are plagued with near-certain disastrous health consequences, citing a host of risks related to incompatibility and blood-borne diseases.12 However, the Society often fails to mention the benefits of transfusion. Interestingly, and perhaps paradoxically, their faith permits the consumption of animal meat and wearing of products made from animal hides. As physicians, we must respect the fact that some people have beliefs that they deem more important than their own lives, but this is not say that those beliefs cannot be questioned, or that patients cannot be encouraged to examine them for themselves.18 LEGAL PARAMETERS In 1914, the landmark case of Schloendorff v. Society of New York Hospital established the right of any adult with capacity to refuse medical treatment.20 It is now commonplace for adult Jehovah’s Witnesses to exercise this right by carrying with them a wallet-sized advance directive card indicating their incontrovertible refusal of blood (Fig. 1). The blood refusal card informs health care personnel that no blood is to be given to the individual, under any circumstance, irrespective of prognosis in the absence of transfusion. This advance directive should be made known to all health care Fig. 1. Jehovah’s Witness blood refusal card (from Associated Jehovah’s Witnesses for Reform of Blood: http://www.ajwrb.org/watchtower/ card.shtml). Volume 65 • Number 1 239 The Journal of TRAUMA威 Injury, Infection, and Critical Care providers at the time of hospitalization, or be executed as soon as practicable thereafter. Laws pertaining to a parent’s right to refuse blood transfusion either for themselves or for their children vary according to state. Each state has a mechanism to seek judicial relief when a parent of a minor child refuses to consent to necessary treatment of him or herself or of a minor. The courts have upheld parents’ decisions to refuse blood transfusion for themselves when the remaining parent, a family member, or a friend would be able to care for a minor child or children if the patient died. The legal power to provide or withhold consent for medical treatment of children who lack capacity falls under the umbrella of parental responsibility, except in the setting of an emergency. A series of court decisions21–23 has clarified that parents do not have the ability to refuse blood on behalf of their children when blood product administration is warranted. Such limitation on parental rights is based on three overarching principles: First, the child’s interests and those of the state outweigh parental rights to refuse medical treatment21; second, parental rights do not give parents lifeand-death authority over their children21,22; and third, parents do not have an absolute right to refuse medical treatment for their children based on their religious beliefs if that refusal is regarded as unreasonable.22,23 However, the ability of some adolescents, or so-called mature minors, to refuse medical treatment is not as clear-cut. Three United States (IL, TN, and WV) recognized the concept of the mature minor, and adolescents in these states are granted the same decision-making rights as adults.24 In the remaining states, adolescents rely on parental decisionmaking, or that of the courts, if necessary. In the case of an emergency, decision-making for the patient can be complicated. Blood refusal cards document informed risks, but do not document that the patient understands the potential benefits. One may argue that a blood refusal card, therefore, cannot be accepted as signed with informed consent, unless a thorough conversation transpires between physician and patient. Whenever possible, physicians should provide the necessary information for an individual to make an informed choice. In the event that such an opportunity is not possible, or if there is any doubt regarding the validity of a blood refusal card, physicians should administer blood products in life-threatening situations. Suicide attempts, severe injuries in minors, or a documented change in religious faith represent circumstances where blood product administration may be considered.24 In complicated cases such as these, there is the possibility of legal action taken against the hospital or health care provider by individuals other than the patients themselves.18 Although Jehovah’s Witnesses are not generally litigious, family members, or nonpracticing Jehovah’s Witnesses may pursue legal action after watching a loved one die from “nontreatment,” regardless of the patient’s documented wishes. As the health care provider, in circumstances where family members do not agree with the patient’s medical deci240 sions, it is important to be aware of the discrepancy and have a thorough discussion with family members and, if possible, hospital patient representatives. EARLY RECOGNITION OF RELIGIOUS AFFILIATION Optimization of patient care for Jehovah’s Witnesses demands early knowledge of the patient’s religious affiliation. Nelson et al.25 reported a 16-year retrospective review of traumatically injured Jehovah’s Witnesses at a Level I trauma center, a group that included 77 patients with 92% blunt and 8% penetrating injuries. The authors observed an “unacceptably” high rate of unrecognized Jehovah’s Witness patients, as the primary physician was aware of patients’ religious affiliations in only 32% of cases. Furthermore, more than one-half of all patients’ charts in this review lacked any documentation of the patients’ religious status by any member of the health care team. Transfusion was administered to only 5% (n ⫽ 4) of Jehovah’s Witness patients; one against the will of an adult patient with capacity, one to a minor under a court order, and two in the trauma room before the patients’ religious status was known. Major changes in therapeutic approach, including early operation, were made in 13% of these patients as a direct result of early determination of religious affiliation. In response to their findings, Nelson et al. recommended that the religious organization should provide members with bracelets or necklaces (“medical alert” style). An additional recommendation was to revise the standard Advanced Trauma Life Support protocol for history taking to include a specific question pertaining to religious or personal objections to blood transfusion. CLINICAL CONSEQUENCE OF TRANSFUSION REFUSAL After proper recognition of Jehovah’s Witnesses in the trauma or critical care setting, the religious beliefs of these individuals beg the pertinent question of whether practicing Jehovah’s Witnesses have an increased risk of death after traumatic injury or surgery. In 2003, Varela et al.26 conducted a retrospective cohort study of 556 patients comparing the risks of death after major trauma for Jehovah’s Witnesses and other religious groups (i.e., Catholics, Baptists, and others). There was no significant difference in mean injury severity score identified among religious groups, nor any statistically significant associations between religion and injury severity score. Significant predictors of mortality were age, systolic blood pressure upon admission, Glasgow Coma Scale score, and type of trauma. After controlling for these predictors of mortality, Varela et al., concluded that Jehovah’s Witnesses had no increased risk of death after major trauma compared with other religious groups. Indeed, the consequences of refusing blood transfusion have been surprisingly anticlimatic, at least for elective surgery. In 1993, Kitchens27 conducted a review of 16 reported series of Jehovah’s Witness patients who were not given blood despite undergoing 1,404 surgical procedures that norJuly 2008 Contemporary Approach to Jehovah’s Witnesses mally require blood transfusion. Severe anemia was implicated as the primary cause of death of eight patients (0.6%), and contributed to the death of 12 additional patients (0.9%). Given that refusal of transfusion by Jehovah’s Witnesses increased the overall operative risk by only 0.5% to 1.5%, Kitchens concluded that such refusal “is not as perilous as anticipated”. Several other studies have corroborated this finding in nontrauma settings, citing no difference in operative morbidity or mortality in Jehovah’s Witnesses compared with non-Jehovah’s Witnesses undergoing cardiac,28 –30 neurologic,31 urologic,32 orthopedic,33,34 and major gynecologic and obstetric surgery,35 even after controlling for preoperative risk factors. In addition to the apparent lack of mortality benefit attributable to transfusion, recent data suggest that Jehovah’s Witnesses may actually benefit with regard to improved clinical outcomes from the decision to forego transfusion. Vincent et al.36 led a multicenter prospective observational cross-sectional study of 3,534 critically ill non-Jehovah’s Witness patients admitted to 146 western European intensive care units (ICU) during a 2-week period in 1999. Paradoxically, the study found that ICU length of stay, organ dysfunction, and overall mortality (29.0% vs. 14.9%) were significantly higher in critically ill patients who underwent transfusion compared with similar nontransfused patients. Kneyber et al.37 reached similar conclusions in a critically ill pediatric population. Jehovah’s Witness cite the risk of contagion as a reason for refusing transfusion, and although very rare, there exists the transmission of disease through blood transfusion. Transfusion has long been associated with the risk of transmission of human immunodeficiency virus and hepatitis C, especially before 1985 when accurate testing was not available. Although the risk of these diseases through transfusion is now very low, there are new infectious agents that pose a threat to the safety of blood transfusion. Protozoa (e.g., Plasmodium) and viruses other than human immunodeficiency virus (e.g., West Nile virus, Severe Acute Respiratory Syndrome coronavirus) are of emerging concern, namely because current testing either does not exist, or may be unreliable.38 There will always be an infectious risk associated with transfusion, and any effort to minimize transfusion will also minimize the risk of transmission of etiologic agents. Considering the rarity with which Jehovah’s Witnesses die from severe anemia after major elective surgery27–35 and that transfusion may actually portend a worse prognosis,36 Carson et al.39 explored the clinical consequences of very low hemoglobin concentration in individuals who decline blood transfusion for religious reasons. The retrospective cohort study included 2,083 patients who underwent surgery and subsequently had a postoperative hemoglobin concentration of 8 g/dL or less. After adjusting for age, cardiovascular disease, and Acute Physiology and Chronic Health Evaluation II score, the odds of death for patients with a postoperative hemoglobin concentration of 8 g/dL or less increased 2.5 times (95% CI, 1.9 –3.2) for each 1 g decrease in hemoVolume 65 • Number 1 globin concentration. However, it was evident that morbidity and mortality rates dramatically increased only when the hemoglobin concentration decreased below 5 g/dL (34% vs. 57.7%, respectively). Many studies have examined the effects of very low hemoglobin concentrations on circulation and cognitive functioning to analyze the “terminal hemoglobin threshold” in human beings.40 – 44 In otherwise healthy individuals, the terminal hemoglobin is unknown but appears to be below 5 g/dL, and may even be as low as 3 g/dL.40 – 42 Cognitive functioning is usually impaired before the effects on global circulation become apparent.40,43 When hemoglobin concentrations are acutely lowered to 5 g/dL, there is no evidence of circulatory insufficiency. However, cognitive functioning and memory begin to decline at hemoglobin concentrations of 6 g/dL and 5 g/dL, respectively.43 These impairments are reversible and resolve with a single transfusion (hemoglobin concentrations ⬎7 g/dL)43 or supplemental oxygen.44 Of note, these studies were conducted in healthy individuals, and there is no accounting for confounding variables (e.g., underlying cardiac disease, medications, sepsis, trauma) that may alter the hemoglobin concentration threshold in critical care patients. The effect of RBC mass on clinical outcome remains controversial. Nikolsky et al.45 conducted a study of 6,929 consecutive patients who were treated with percutaneous coronary intervention. Of the 6,929 patients, 1,708 (24.6%) had anemia according to criteria of the World Health Organization (hematocrit ⬍39% for men and ⬍36% for women). Anemic patients had significantly higher mortality rates during hospitalization and at 1 year (1.9% vs. 12.8%) compared with those who did not have anemia (0.4% vs. 3.5%). After adjusting for age, gender, diabetes mellitus, creatinine clearance, and congestive heart failure, low baseline hematocrit remained a significant predictor of a 1-year increased mortality risk. Conversely, Rao et al.46 analyzed clinical data from over 24,000 patients hospitalized for acute coronary syndrome across three large international trials and found transfusion in patients with higher hematocrit levels to be associated with increased 30-day mortality. The authors cautioned against the routine use of blood transfusion to maintain arbitrary hematocrit levels in stable patients given that the association between transfusion and increased 30-day mortality was observed only in patients with nadir hematocrit levels above 25%; no such association was observed in patients with nadir hematocrit levels of 25% or less. In addition, mild degrees of both preoperative anemia and polycythemia have been associated with an increased risk of 30-day postoperative mortality and cardiac events in noncardiac surgical patients.47 Blood transfusion has also been shown to be a significant risk factor for the development of infection in critically ill patients48 –50 and to increase the occurrence of postoperative atrial fibrillation after cardiac surgery.51 Thus, the literature supports the tenets that blood transfusion may 241 The Journal of TRAUMA威 Injury, Infection, and Critical Care Fig. 2. The Watchtower Bible and Tract Society’s current classification of blood products by acceptability. have risks and benefits, depending on the clinical circumstance and patient demographics. CONTEMPORARY STRATEGIES IN THE CLINICAL MANAGEMENT OF JEHOVAH’S WITNESSES The clinical management of Jehovah’s Witness patients in a trauma, surgical, or critical care setting requires a high index of suspicion and an aggressive and multidisciplinary approach. Immediate intervention (including the decision to operate early), effective identification of bleeding, minimizing iatrogenic and intraoperative blood loss, enhancing RBC production, ensuring adequate hemostasis, and maintaining intravascular volume and are all important strategies to incorporate into the care of a Jehovah’s Witness patient. The Watchtower recently repeated the long-standing religious position of Jehovah’s Witnesses, stating that the acceptance of allogeneic whole blood and its four primary components (i.e., RBCs, white blood cells, platelets, and plasma) violates Jehovah’s law.52 However, the steadfast views of this religious group appeared to be in flux following a second article,53 published in the same 2004 edition of The Watchtower, entitled “Be Guided by the Living God,” which redefined the guidelines for use of blood products. The article detailed the rules regarding which blood products are “unacceptable” and which are for the “Christian to decide.” Moreover, the article featured a newly developed chart that clearly demarcated the acceptability of various blood products, including minor fractions derived from blood (Fig. 2). Potentially acceptable blood fractions include albumin, rHuEPO, clotting factor concentrates, and oxygen therapeutics. Solid organ and stem cell transplantation is an additional treatment modality debated within the Jehovah’s Witness community. Whereas some accept transplantation as a therapeutic option, many think that it falls within the guidelines set forth by the Blood Ban. The following represent key components in the current management of patients who elect to forego blood transfusion (Table 1). Albumin The use of albumin in the critical care setting remains a controversial issue. Whereas the properties of albumin portend several potential therapeutic benefits, including maintenance of plasma oncotic pressure, protective effects on the microcirculation, antioxidant and scavenger activities, and 242 Table 1 Strategies in the Clinical Management of Jehovah’s Witness Patients Strategy Minimize iatrogenic blood loss Minimize intraoperative red blood cell loss Enhance red blood cell production Ensure hemostasis, prophylactic or therapeutic Maintain blood volume Methods of Achievement Elimination of unnecessary phlebotomy Reduction of test sample volume Meticulous surgical technique Isovolemic hemodilution Hypervolemic hemodilution Intraoperative blood salvage “Bloodless” surgery Recombinant human erythropoietin (rHuEPO) Supplemental iron, vitamin B12, and folate Early operative intervention Correction of coagulopathies Desmopressin Antifibrinolytic agents Aprotinin Recombinant human factor VIIa Crystalloid solutions Synthetic colloid solutions anticoagulant effects, its utility relative to survival benefit has yet to be demonstrated. Two meta-analyses have broadly investigated effects of albumin administration in heterogenous populations of critically ill patients.54,55 Neither of these reports could detect a survival benefit with the use of albumin, with the earlier report54 even noting a 6% increase in mortality among albumin recipients. Moreover, a recent multicenter, double-blind, randomized, trial56 found no difference in mortality between ICU patients receiving either 4% albumin or normal saline for fluid resuscitation. The trial concluded that albumin and saline should be considered clinically equivalent treatments for intravascular volume resuscitation, albeit in a heterogenous study population, and selection of resuscitation fluid should be guided by its safety, tolerability, and cost. Given the paucity of evidence for clinical benefit, the routine use of albumin, either in critically ill patients at large or in the consenting Jehovah’s Witness, does not appear to be economically justifiable at the present time. Recombinant Human Erythropoietin Erythropoietin is a hormone produced by the kidneys that stimulates bone marrow to produce RBCs. The rationale July 2008 Contemporary Approach to Jehovah’s Witnesses for therapy with rHuEPO, an albumin-containing product, involves increased erythropoiesis resulting in a higher hemoglobin concentration and the subsequent reduction in the need for RBC transfusion. Treatment with rHuEPO may be an option in a Jehovah’s Witness patient, depending on their individual belief regarding receipt of albumin or albumincontaining products. In addition, RBC production may be augmented further by supplementary iron, vitamin B12, and folate therapy, as indicated. A prospective, randomized, double-blind, placebo-controlled, multicenter trial conducted by Corwin et al.57 demonstrated that a weekly dosing schedule of rHuEPO was associated with an increase in hemoglobin concentration and a corresponding significant reduction in the rate of allogeneic RBC transfusion. Several studies have investigated the most efficacious dose of rHuEPO. Recently, Georgopoulos et al.58 assessed the efficacy of two rHuEPO dosing schedules (group A: iron ⫹ rHuEPO 40,000 U weekly; group B: iron ⫹ rHuEPO 40,000 U thrice weekly) compared with controls (group C: iron saccharate only). The dose-response study found that the cumulative number of RBC units transfused, average number of RBC units transfused per patient and per transfused patient, average volume of RBCs transfused per day, and percentage of transfused patients were significantly higher in the control group than in either experimental group. Although Georgopoulos et al. demonstrated a significant reduction in the need for RBC transfusion with rHuEPO therapy, the magnitude of the reduction did not differ between the two dosing schedules. However, a dose-dependent response of hematocrit and hemoglobin concentrations to rHuEPO was observed, and the administration of rHuEPO to critically ill patients at a dose of 40,000 U thrice weekly was deemed safe and efficacious. Nevertheless, conflicting clinical and biochemical findings suggest that rHuEPO therapy may be ineffective in critically ill patients, who often have increased concentrations of endogenous EPO, a finding that challenges the utility of supplementing EPO stores that are otherwise intact.59,60 In addition, abnormal iron metabolism in critically ill patients (i.e., iron deficiency or decreased iron availability secondary to sequestration) limits optimal erythropoiesis even in the setting of adequate endogenous and exogenous EPO.61,62 Moreover, critical illness is complicated by a surge of proinflammatory cytokines, which compounds the defective erythropoiesis via decreasing production and survival of RBCs, bone marrow suppression, decreased iron availability, and reduced production of EPO.63 factor VIIa. Initially approved for the treatment of bleeding in hemophilia patients,64 Recombinant human activated factor VIIa (NovoSeven, Novo Nordisk Pharmaceuticals, Princeton, NJ) has received much attention in recent years for its proposed use as an adjuvant therapy in the control of hemorrhage, and thus may serve as a useful clinical tool in the treatment of Jehovah’s Witness trauma, surgical, or critical care patients. Intravenously administered recombinant activated factor VIIa (rFVIIa) binds to tissue factor at the site of endothelial injury, thereby triggering a local coagulation process that begins with the production of thrombin and subsequent platelet activation. The surface of activated platelets serves as a scaffold for rFVIIa to potentiate the activation of the coagulation cascade, directly or indirectly.65,66 Hemostasis is achieved upon the generation of additional thrombin, with stability of clot formation conferred by rFVIIa-mediated activation of thrombin-activated fibrinolysis inhibitor.67 The hemostatic capabilities of rFVIIa have been applied to trauma patients with massive hemorrhage and coagulopathy since 1999.68 In a double-blind randomized controlled trial, Boffard et al.69 reported that use of rFVIIa as an adjuvant therapy was associated with a significant decrease in RBC transfusion requirements in blunt trauma patients surviving 48 hours or more. Similar but less dramatic trends were observed in cases of penetrating trauma. Two recent reports from the Australian and New Zealand hemostasis registry offered similar support for the use of rFVIIa in trauma.70,71 Whereas trends toward a reduction in mortality and critical complications have been observed, the only randomized controlled trial to date69 reported no significant difference in mortality between trauma patients who received rFVIIa and those who received placebo. A retrospective review of 5,334 combat trauma patients requiring massive transfusion also showed no survival benefit in patients receiving rFVIIa, independent of timing of rFVIIa administration.72 Nevertheless, early administration of rFVIIa (within 4 hours of onset) was shown to reduce mortality and improve functional outcome in patients developing acute intracerebral hemorrhage.73 In addition, one case report describes the successful perioperative use of rFVIIa in a warfarin-anticoagulated Jehovah’s Witness patient with an acute subdural hematoma after undergoing surgical evacuation without excessive blood loss.74 A multicenter, multinational prospective randomized trial is currently underway to better elucidate the efficacy of rFVIIa in trauma patients and the optimal timing of therapy initiation.75 Recombinant Human Activated Factor VIIa Hemoglobin-Based Oxygen Carriers Correction of coagulopathies is central to ensure either prophylactic or therapeutic hemostasis. Given that some Jehovah’s Witnesses may refuse fresh frozen plasma or cryoprecipitate, several alternatives may be used in the setting of actual or expected hemorrhage, including aprotinin, antifibrinolytics, desmopressin, and recombinant human activated A primary goal in any trauma or surgical patient is to maintain adequate intravascular volume. Traditionally, maintenance of blood volume is achieved with crystalloid solutions and blood products. In Jehovah’s Witnesses, however, allogeneic blood products are not permissible, and crystalloid may be insufficient by itself to maintain adequate oxygen Volume 65 • Number 1 243 The Journal of TRAUMA威 Injury, Infection, and Critical Care delivery. As a result, the development of a “perfect” blood substitute, or synthetic colloid solution, is of great interest.76 Such a product would have definite advantages over human RBCs, including rapid and widespread availability; fewer requirements with regard to storage, transport, and compatibility testing; a longer shelf life; and a more consistent supply. An ideal substitute would be less antigenic than allogeneic RBCs, and would have less risk of disease transmission. In addition, one would have the ability to treat patients who refuse standard blood transfusions. Within the classic construct of transfusion medicine, the general role of blood is to supply oxygen to tissues via hemoglobin. Accordingly, early attempts in the 1940s to develop blood substitutes were focused on a simple cell-free solution of hemoglobin.77 Investigations showed that unmodified cell-free hemoglobin had limitations; namely, its oxygen affinity was too high for effective tissue oxygenation, its half-life within the intravascular space was too short to be useful clinically, and its tendency to dissociate into dimers caused renal tubular injury.76 Various types of hemoglobin modification methods (e.g., purification, cross-linkage, polymerization) were developed more recently to overcome these obstacles.77 Efficiency of cross-linked hemoglobin to transport and unload oxygen was confirmed in a variety of animal shock models; modified hemoglobin solutions improve tissue oxygenation at a rate similar to that of infusion of allogeneic blood products.78 The use of two cross-linked polymers of bovine (Hemopure, Biopure, Cambridge, MA) and human (PolyHeme, Northfield Laboratories, Evanston, IL) origin are beginning to be integrated into cardiac and abdominal surgery as well as trauma care.79 – 82 The intravascular half-life of the polymerized form of bovine hemoglobin solution (PBH) is approximately 24 hours, and its excretion is nonrenal. Administration of PBH results in vasoconstrictive effects that may also increase systemic and pulmonary vascular resistance, with a resultant decrease in cardiac index. As such, this product is recommended to serve as a bridge until either donor blood becomes available or the patient’s endogenous RBCs undergo active regeneration.83 The PBH solution is currently undergoing phase III clinical trials as a perioperative alternative to RBC transfusion in orthopedic surgery in the United States, the European Union, Canada, and South Africa. Notably, Hemopure has been approved for human use and commercial sale in South Africa since April 2001, unique for this product class. Additionally, the U.S. Naval Medical Research Center was granted $4 million in Congressional funding for the U.S. Navy to continue research and development of PBH.84 PolyHeme (PHH) is derived from pyridoxylated polymerized outdated hemoglobin from human blood, with an intravascular half-life of 24 hours and a shelf life of longer than 12 months (refrigerated). In a phase II randomized trial comparing the therapeutic benefit of PHH with that of allogeneic RBCs, PHH reduced the required number of allogeneic RBC transfusions in patients with acute trauma.81,82 No 244 adverse clinical events, including vasoactive properties, were observed in this trial. Currently, this product is undergoing phase III studies for the treatment of patients with substantial acute blood loss. In general, hemoglobin-based oxygen carriers (HBOCs) reduce or eliminate the need for allogeneic blood transfusions in patients undergoing orthopedic surgery, elective abdominal surgery, and coronary artery bypass graft surgery.76,81,83,85,86 If HBOCs are approved for such use, Jehovah’s Witnesses may benefit from a rapidly available universal oxygen-carrying volume expander, and HBOCs may serve as a bridge in the temporary support of a patient who will not accept blood products. The major limitation of HBOCs still relates to their short intravascular half-life, whereas a transfused RBC can persist in the circulation for several weeks in a patient with no active bleeding or hemolysis. Given that utilization of an HBOC requires frequent readministration, they would be costly as a definitive replacement for blood. Acute Normovolemic Hemodilution Acute normovolemic hemodilution (ANH), or intraoperative hemodilution, has been advocated as a safe, easy, and inexpensive method to avoid exposure to allogeneic blood since the 1970s.87 This blood conservation technique involves withdrawing blood from a patient into standard collection bags before or shortly after induction of anesthesia, with maintenance of normovolemia using simultaneous infusion of crystalloid or colloid replacement. Circulating blood volume remains constant given that the reduction in red cell mass is compensated by the increase in plasma volume, and the patient’s blood can be reinfused at any time during or after surgery. A recent meta-analysis of prospective, randomized controlled studies of ANH determined that this blood conservation technique decreases the likelihood of exposure to allogeneic blood and the volume of blood transfused.88 However, heterogeneity exists among study results and the overall benefit of ANH remains inconclusive at this time. Nevertheless, a recent review notes that ANH achieves similar outcomes at lower cost compared with autologous predonation and, if combined with other pharmacologic strategies, may eliminate future use of allogeneic blood transfusion entirely for elective surgery.89 Several other theoretical advantages of ANH have been described.90 –92 For instance, the circulating blood in ANH has a lower hematocrit; therefore, blood loss represents a saving relative to quantitative red cell mass. ANH is also associated with reduced blood viscosity, thereby reducing systemic vascular resistance and allowing for an increase in cardiac output without an increase in myocardial oxygen consumption. In addition, reinfusion of withdrawn blood exposes patients to a large volume of their own platelets and coagulation factors, thus preserving the patient’s inherent coagulation function. July 2008 Contemporary Approach to Jehovah’s Witnesses Autologous Autotransfusion In addition to the four primary components of allogeneic blood, Jehovah’s Witnesses also reject any autologous blood that has been separated from the body. These prohibitions, however, do not prevent most Jehovah’s Witnesses from consenting to the use of blood management techniques and procedures involving temporary diversion of autologous blood as long as no allogeneic blood is used (i.e., cardiopulmonary bypass, dialysis, intraoperative blood salvage, and reinfusion). Although the lay person may not discern a difference between these interventions and autologous blood that has been separated from the body, Jehovah’s Witnesses distinguish the acceptability of such therapy on the basis of whether the diverted blood remains part of the circulatory system. The majority of Jehovah’s Witnesses, for example, think that the extracorporeal tubing utilized in cardiopulmonary bypass, dialysis, or cell salvage equipment represents an extension of their own circulatory system provided that the tubing remains continuous with the patient’s intravascular compartment. The acceptance of autologous donation and retranfusion technology remains at the discretion of each individual patient. Conventional cell saver autotransfusion is not accepted by all Jehovah’s Witnesses because the salvaged blood is processed in batches, thereby interrupting the continuity of the blood with the body. However, newer modalities permit continuous processing of salvaged blood, and therefore are able to achieve an uninterrupted flow of RBCs back to the patient. Whereas in principle a continuous circuit can be expensive and require relatively sophisticated equipment, its use enhances control of sterility and reduces the amount of allogeneic blood transfusions required by patients. Transplantation The use of solid organ and stem cell transplantation therapy is also debated within the Jehovah’s Witness community. Whereas some consider transplantation to fall under the guidelines set forth by the Blood Ban, many Jehovah’s Witnesses will accept these treatment modalities as long as allogeneic blood components are removed from the process. The first case of a solid organ transplantation of a Jehovah’s Witness took place at University of California, Los Angeles in 1986.93 Since then, numerous other cadaveric and living donor transplants have been published in this patient population, including liver,94 kidney,95 pancreas,95 and lung.96 Solid organ transplantation often requires a large surgical dissection and suturing of major vessels. Moreover, patients requiring liver transplantation are often at a higher risk of bleeding because of coagulation disturbances resulting from cirrhosis and portal hypertension, thrombocytopenia, altered platelet-vessel interaction, low levels of coagulation factors, and arterial and venous collaterals.97 Consequently, if any solid organ transplantation is going to be considered in a Jehovah’s Witness patient that will not accept transfusion, Volume 65 • Number 1 stringent patient selection and vigilant preoperative, intraoperative, and postoperative blood management is essential for success in these patients. Some Jehovah’s Witness patients also accept allogeneic hematopoietic stem cell transplantation. As with solid organ transplantation, the stipulation for accepting this treatment is that it be “bloodless”, or without the transfusion of RBCs, platelets, or plasma. There is a growing body of literature supporting the feasibility of “bloodless transplants” in properly selected patients, given that the procedures are performed with meticulous attention to blood conservation and supportive care. The willingness to accept allogenic hematopoietic stem cells while denying the progeny of those stem cells is potentially a conflicted argument. The decision to accept transplantation of any kind is left to the individual member, and falls in line with the decision of whether or not to accept albumin, rHuEPO, immunoglobulins, and factor concentrates. As with whole blood fractions, it is unclear as to the line that separates acceptable treatments from those that are against the tenets of the religion. This emphasizes further that the belief system of Jehovah’s Witnesses is in flux, and the absolute guidelines for treatment are becoming blurred. CONCLUSION Jehovah’s Witnesses represent a unique and sometimes frustrating challenge to the medical field. As physicians, it is important to understand the basis for their collective beliefs and the choices they make in the medical realm. It is equally important to understand the circumstances in which it may be appropriate to pursue alternative means of care and that the need for transfusion is often overestimated. The “terminal hemoglobin threshold” may be as low as 3 g/dL to 5 g/dL in some patients, and transfusion alone is not without potential deleterious physiologic effects. Given the ethical and legal dimensions associated with the contemporary care of the Jehovah’s Witness patient, a low threshold is necessary when deciding when, and if, to utilize available hospital resources. The belief system of this religious group appears to be in a state of flux, specifically concerning the Blood Ban and its application. Effective patient-physician communication is necessary to elucidate the best avenue of care for all parties involved. REFERENCES 1. Anonymous. 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Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: results of a randomized, double-blind trial. J Thorac Cardiovasc Surg. 2002;124:35– 42. Sprung J, Kindscher JD, Wahr JA, et al. The use of bovine hemoglobin glutamer-250 (Hemopure) in surgical patients: results of a multicenter, randomized, single-blinded trial. Anesth Analg. 2002; 94:799 – 808. Gould SA, Moore EE, Hoyt DB, et al. The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery. J Am Coll Surg. 1998;187:113–120. Gould SA, Moore EE, Hoyt DB, et al. The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable. J Am Coll Surg. 2002;195:445– 452. Levy JH. The use of haemoglobin glutamer-250 (HBOC-201) as an oxygen bridge in patients with acute anaemia associated with surgical blood loss. Expert Opin Biol Ther. 2003;3:509 –517. Biopure Corporation. Biopure. 2007. Available at: http:// www.biopure.com. Accessed September 22, 2007. Reid TJ. Hb-based oxygen carriers: are we there yet? Transfusion. 2003;43:280 –287. Greenburg AG, Kim HW. Hemoglobin-based oxygen carriers. Crit Care. 2004;8:S61–S64. Messmer K. Hemodilution. Surg Clin North Am. 1975;55:659 – 678. Bryson GL, Laupacis A, Wells GA. Does acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A metaanalysis. The International Study of Perioperative Transfusion. Anesth Analg. 1998;86:9 –15. Monk T. Acute normovolemic hemodilution. Surg Infect. 2005; 6:S9 –S15. Baldry C, Backman SB, Metrakos P, Tchervenkov J, Barkun J, Moore A. Liver transplantation in a Jehovah’s Witness with ankylosing spondylitis. Can J Anaesth. 2000;47:642– 646. Matot I, Scheinin O, Jurim O, Eid A. Effectiveness of acute normovolemic hemodilution to minimize allogeneic blood transfusion in major liver resections. Anesthesiology. 2002;97:794 – 800. Goodnough LT, Monk TG, Brecher ME. Acute normovolemic hemodilution should replace the preoperative donation of autologous blood as a method of autologous-blood procurement. Transfusion. 1998;38:473– 476. Corno AF, Laks H, Stevenson LW, Clark S, Drinkwater DC. Heart transplantation in a Jehovah’s Witness. J Heart Transplant. 1986; 5:175–177. Jabbour N, Gagandeep S, Mateo R, et al. Live donor liver transplantation: staging hepatectomy in a Jehovah’s Witness recipient. J Hepatobiliary Pancreat Surg. 2004;11:211–214. Boggi U, Vistoli F, Del Chiaro M, et al. Kidney and pancreas transplants in Jehovah’s witnesses: ethical and practical implications. Transplant Proc. 2004;36:601– 602. Conte JV, Orens JB. Lung transplantation in a Jehovah’s Witness. J Heart Lung Transplant. 1999;18:796 – 800. Detry O, Deroover A, Delwaide J, et al. Avoiding blood products during liver transplantation. Transplant Proc. 2005;37:2869 –2870. 247 Recombinant Human Erythropoietin Therapy in Critically Ill Jehovah’s Witnesses Amanda M. Ball, Pharm.D., and P. Shane Winstead, Pharm.D. Blood transfusions and blood products are often given as a life-saving measure in patients with critical illness. However, some patients, such as Jehovah’s Witnesses, may refuse their administration due to religious beliefs. Jehovah’s Witnesses accept most available medical treatments, but not blood transfusions or blood products due to their religion’s interpretation of several passages from the Bible. Since recombinant human erythropoietin (rHuEPO) became available, several cases have been reported in which rHuEPO was successfully administered to critically ill Jehovah’s Witnesses. Administration of rHuEPO in combination with other blood conservation techniques has been shown to increase hemoglobin levels and survival in patients who experienced trauma, burns, general surgery, or gastrointestinal hemorrhage. We performed a literature search of the MEDLINE and International Pharmaceutical Abstracts databases of rHuEPO therapy in the Jehovah’s Witness population. Fourteen cases were identified in which rHuEPO was administered to Jehovah’s Witnesses who required the drug for critical care resuscitation as an alternative to blood products. In each clinical situation, rHuEPO enhanced erythropoiesis; however, time to the start of treatment, dosages, route of administration, and treatment duration varied widely. Supplementation with adjunctive agents, such as iron, folic acid, and vitamin B12, was also beneficial. Use of rHuEPO in Jehovah’s Witnesses may provide an alternative to blood transfusions or blood products. Other alternatives, such as hemoglobin-based oxygen carriers and perfluorocarbons, are also being explored. Key Words: erythropoietin, rHuEPO, Epogen, Jehovah’s Witness, hemorrhage. (Pharmacotherapy 2008;28(11):1383–1390) OUTLINE Published Reports of Jehovah’s Witnesses Treated with Recombinant Human Erythropoietin for Off-Label Indications Trauma Burns General Surgery Gastrointestinal Hemorrhage Adjunctive Therapy with Iron, Folic Acid, and Vitamin B12 Alternative Therapy with Hemoglobin-Based Oxygen Carriers and Perfluorocarbons Recommended Use of Recombinant Human Erythropoietin in Jehovah’s Witnesses Conclusion From the Department of Pharmacy, the Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania (Dr. Ball); and Pharmacy Services, UK Healthcare, and the Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, Kentucky (Dr. Winstead). Address reprint requests to Amanda M. Ball, Pharm.D., Department of Pharmacy, Basement Silverstein, 3400 Spruce Street, Philadelphia, PA 19104. Blood transfusions and blood products are often given as a life-saving measure in patients with critical illness. However, some patients, such as Jehovah’s Witnesses, may refuse their administration due to religious beliefs. Jehovah’s Witnesses are followers of a Christian religion, with about 5.5 million practicing members worldwide. They accept most available medical 1384 PHARMACOTHERAPY Volume 28, Number 11, 2008 treatments, but not blood transfusions or blood products due to the religion’s interpretation of several passages from the Bible. United States courts have consistently supported the adult patient’s decision to refuse blood on the basis of religious beliefs.1 Thus, clinicians are obligated to respect patients’ preferences, and alternatives to blood transfusions and blood products are needed. In Jehovah’s Witnesses, the mainstay of treatment of hemorrhage is blood conservation, and a number of techniques are used to minimize blood loss in this patient population. Techniques include perioperative blood salvage from autotransfusion of blood, prevention of intraoperative blood loss through surgical technique, induced hypotension, and correction of coagulopathy. Minimizing phlebotomy and iatrogenic blood loss in intensive care patients is another important blood conservation technique. Oxygen demand and consumption can be minimized through sedation, paralysis, mechanical ventilation, and possibly hypothermia, along with maximizing oxygen delivery through administration of inotropes or using hyperbaric oxygen chambers.2 With use of these blood conservation techniques, patients have survived with extremely low hemoglobin levels without enhanced erythropoiesis. In 1989, recombinant human erythropoietin (rHuEPO) received approval from the United States Food and Drug Administration for treatment of anemia associated with chronic renal failure. The drug is a 165–amino acid glycoprotein that stimulates red blood cell production in the same manner as endogenous erythropoietin. Other treatment indications approved by the FDA include anemia due to chronic kidney disease, anemia secondary to zidovudine therapy in patients with human immunodeficiency virus infection, anemia secondary to cancer chemotherapy, and reduction of allogeneic blood transfusions during surgery. The drug also has been used for many off-label indications. Many Jehovah’s Witnesses have accepted rHuEPO as a treatment option to maintain and enhance erythropoiesis even though the vial contains albumin. The drug has been administered with success in critically ill Jehovah’s Witnesses for numerous hemorrhagic conditions. To gain a better understanding of the use of rHuEPO in Jehovah’s Witnesses who required the drug for critical care resuscitation as an alternative to blood products, we conducted a literature search of the MEDLINE and International Pharmaceutical Abstracts databases. Search terms were Jehovah’s Witness and erythropoietin, epoetin, Epogen, Procrit, and darbepoeitin; only reports published in English and concerning adult human patients were identified. The search yielded 32 articles; however, 18 were excluded because the patients had been treated with rHuEPO for FDA-approved indications, such as oncology and elective surgery, or the patients did not receive rHuEPO for critical care resuscitation as an alternative to blood products (e.g., pregnant women). Thus, 14 case reports were reviewed in detail. These critically ill Jehovah’s Witnesses had experienced trauma, burns, general surgery, or gastrointestinal hemorrhage and were treated with rHuEPO as a potentially life-sustaining measure as an alternative to blood transfusions or products. Published Reports of Jehovah’s Witnesses Treated with Recombinant Human Erythropoietin for Off-Label Indications Trauma Prevention and management of hemorrhagic shock due to traumatic injury without administration of blood and blood products are extremely difficult and have led to the administration of rHuEPO with fluids, intravenous iron, and polymerized blood substitute products. Since 1990, several reports have been published regarding rHuEPO administration in Jehovah’s Witnesses with acute traumatic injury. Successful rHuEPO treatment was described in a 36-year-old woman who was involved in a motor vehicle accident and sustained bilateral hemothoraces, left acetabular fracture, and several pelvic fractures.3 On day 7 of hospitalization, the patient’s hemoglobin level and hematocrit had declined to 4.6 g/dl and 14%, respectively; intravenous rHuEPO was started at 300 units/kg/day for 3 days, followed by 150 units/kg subcutaneously 3 times/week for 14 days. Her hematocrit climbed steadily to almost 40% by day 30, with an absolute change of greater than 26% with rHuEPO administration. A 45-year-old woman sustained several traumatic injuries after a train accident and required a splenectomy.4 On day 7, the patient started receiving rHuEPO 36,000 units given over 1 week (route of administration not reported). Her hemoglobin level declined to 3.2 g/dl by hospital day 16 (likely due a tracheostomy performed on day 13). However, by day 44, her hemoglobin level increased by almost 5 g/dl to RECOMBINANT HUMAN ERYTHROPOIETIN FOR JEHOVAH’S WITNESSES Ball and Winstead 1385 greater than 8 g/dl. A 48-year-old man was given intravenous rHuEPO 4750 units/day (50 units/kg/day) starting 10 hours after hospital admission secondary to traumatic injuries sustained in an airplane crash; his hemoglobin level was 6.8 g/dl. 5 On hospital day 3, due to a continued decline in his hemoglobin level to 3.0 g/dl, his daily dose of intravenous rHuEPO was increased to 28,500 units (300 units/kg). This daily dose was maintained until day 13, then the frequency was decreased to every other day for a total of five doses. The patient was discharged with a hemoglobin level of 11.3 g/dl on day 54. The resulting absolute change in hemoglobin level after rHuEPO therapy was 4.5 g/dl. Use of an extremely high dose of rHuEPO was described in a 51-year-old woman involved in a motor vehicle accident.6 On hospital admission, the patient’s hematocrit was 12%; treatment with rHuEPO was started immediately, along with albumin, cryoprecipitate, vitamin K, and suppression of menses. The rHuEPO dosage was 20,000 units given intravenously every other day. When the patient’s hematocrit declined to 7%, the dosage was increased to 7000 units every 8 hours, and intravenous iron was added. The patient’s hematocrit increased to 35% (absolute change of 28%), and she was transferred to a long-term care facility after 30 days of rHuEPO treatment. She subsequently died as a result of her injuries. The highest weight-based rHuEPO dose reported was given to a 44-year-old woman who was involved in a motor vehicle accident and sustained a temporal subarachnoid hemorrhage, facial fractures, rib fractures, and a splenic laceration.7 Treatment with a hemoglobin-based oxygen carrier and rHuEPO 600 units/kg/day (route of administration not reported) was started within 24 hours of the injury and was continued for 2 days. The dosage was subsequently decreased to 300 units/kg/day for 3 days. By hospital day 19, the patient’s hemoglobin increased from 3.2 to 9.8 g/dl (absolute change of 6.6 g/dl). A 67-year-old man involved in a motor vehicle accident started receiving intravenous rHuEPO 48,000 units/day (weight not reported) on hospital day 2 when his hemoglobin level decreased to 3 g/dl.2 The patient also received iron, folic acid, and vitamin B12. In addition, induced hypothermia, minimization of phlebotomy, and aggressive fluid resuscitation with hetastarch and crystalloids were implemented. These techniques and the use of rHuEPO resulted in an absolute change in hemoglobin level of 4.9 g/dl, and at discharge on hospital day 47, the patient’s hemoglobin level was 7.9 g/dl. These six cases represent, to our knowledge, the only current published reports of rHuEPO use in Jehovah’s Witnesses with traumatic injuries. Despite the small number of cases, each patient’s hemoglobin level increased with rHuEPO therapy. Starting dosages ranged from 50–600 units/kg/day, and all six patients received iron supplementation. Furthermore, in each report, intravenous rHuEPO was started during the initial stages of critical illness and, in some cases, transitioned to subcutaneous administration. Intravenous administration may avoid alterations in absorption and the delay to onset seen with subcutaneous administration. The rHuEPO dosage administered in these Jehovah’s Witnesses with traumatic injury varied widely. In addition, the time at which rHuEPO therapy was started also varied, from less than 24 hours to 7 days after the injury. Given the variation in these reports, the time to start and the dosage of rHuEPO therapy in patients with traumatic injury should be individualized and based on severity of injury and decline in hemoglobin level. Burns Two case reports describe use of rHuEPO in patients with burns. The first involved a 52-yearold man with 15% burns on his face and hands.8 On admission, the patient’s hemoglobin level and hematocrit were 15.4 g/dl and 45%, respectively. However, after grafting the patient’s hands only, his hemoglobin level decreased significantly, to 8.0 g/dl, and hematocrit decreased to 24%. Blood loss was anticipated as further grafting procedures were performed. Administration of rHuEPO was begun on hospital day 10. Success was achieved with a dosage of 300 units/kg/day intravenously for 7 days, followed by 150 units/kg subcutaneously 3 times/week for another 3 weeks. The patient’s hemoglobin level increased by 3 g/dl. The second report described a 71-year-old woman with 18% burns over her total body surface area. 9 On admission, the patient’s hemoglobin level and hematocrit were 12 g/dl and 38%, respectively. By hospital day 14, her hemoglobin level had declined to 7 g/dl. Treatment with rHuEPO was begun on hospital day 15 with a non–weight-based dosage of 4000 units subcutaneously 3 times/week for 19 days. 1386 PHARMACOTHERAPY Volume 28, Number 11, 2008 Several skin grafts were performed, and the patient’s hemoglobin level at discharge remained unchanged at 7 g/dl. In both of these patients with burns, rHuEPO therapy was successful. However, the dosage and duration of rHuEPO treatment were extremely different between the two patients. In addition, the maximum dose (300 units/kg/day) was still lower than the doses given to trauma patients. The first patient with burns experienced benefit from rHuEPO treatment whereas the second patient experienced a neutral effect. Of note, only the first patient received iron supplementation and weight-based rHuEPO dosing. General Surgery Use of postoperative rHuEPO in two patients who had undergone gastrointestinal surgery was reported in a case series.10 Both were successfully managed with rHuEPO and adjunctive agents. The first patient was a 55-year-old woman who underwent a subtotal colectomy and Brooke’s ileostomy for ulcerative colitis. Two days after surgery, her hemoglobin level had decreased from 13.6 to 2.8 g/dl, and treatment was begun with intravenous rHuEPO 10,000 units/day plus subcutaneous rHuEPO 10,000 units/day (280 units/kg/day). This dosage was continued until hospital day 16, when her hemoglobin level had increased to 4.8 g/dl; her rHuEPO dosage was then reduced to 10,000 units/day subcutaneously (140 units/kg/day). At discharge, her hemoglobin level had increased to 10.4 g/dl. The total duration of rHuEPO treatment was not provided; however, it was estimated to be more than 30 days, and the result was an absolute change in hemoglobin level of 7.6 g/dl. The second patient was a 43-year-old man who underwent endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy.10 His initial hemoglobin level was 11.1 g/dl; however, 18 days after surgery, it had decreased to 4.6 g/dl. Therapy with subcutaneous rHuEPO 5000 units/day (60 units/kg/day) was started. By day 32 after surgery, the patient’s hemoglobin level had increased to 6.5 g/dl; the rHuEPO dosage was reduced to 5000 units 3 times/week. At hospital discharge, the patient’s hemoglobin was 10.5 g/dl (absolute change 5.9 g/dl). This case series described the only two known reports in which patients were treated with rHuEPO after undergoing general surgery. Because only two patients were involved and the rHuEPO dosages varied widely (60–280 units/ kg/day), one cannot draw conclusions regarding the most appropriate rHuEPO dosage for this population. Ultimately, both patients reached similar hemoglobin level end points (10.4 and 10.5 g/dl) even though therapy was started at very different times (day 2 vs 18 after surgery). Gastrointestinal Hemorrhage The mainstay of treatment for gastrointestinal hemorrhage involves the repair or resection of the source of bleeding, administration of proton pump inhibitors, and blood transfusions as needed. We identified four reports of Jehovah’s Witnesses who received rHuEPO for this lifethreatening bleeding. A 66-year-old woman with four shallow 0.5-cm ulcers in the peripyloric and bulbar region had a hematocrit of 18%. 11 Although no active bleeding was noted, the patient’s hematocrit dropped to 14.5% on hospital day 3. Intravenous rHuEPO 20,000 units/day for 3 days was started, followed by 6500 units every other day. By day 14, her hematocrit had increased to 27.1% (absolute change 12.6%). The second report involved a 63-year-old man with a duodenal ulcer. 10 On admission, his hemoglobin level was 4.8 g/dl. On day 15, his hemoglobin level had further decreased to 4.4 g/dl; he was given rHuEPO 4000 units/day (50 units/kg) subcutaneously, which resulted in a final hemoglobin level of 6.2 g/dl (absolute change in hemoglobin level 1.4 g/dl) over the next 12 days. In the third report, rHuEPO was administered to a 50-year-old woman for treatment of gastrointestinal hemorrhage who had been receiving rHuEPO 3000 units intravenously 3 times/week for anemia due to chronic kidney disease.12 Before the gastrointestinal hemorrhage occurred, the patient’s hematocrit was 33%, which decreased to 18.4% on admission. When her hematocrit decreased to 10.4%, her dosage of subcutaneous rHuEPO was increased to 10,000 units (130 units/kg) 3 times/week and eventually to 20,000 units (260 units/kg) 3 times/week. The patient received approximately 1200 units/kg in week 1, 1670 units/kg in week 2, and 270 units/kg each week thereafter. Her hematocrit rose from 10.4% to 38.5% (absolute change of 28.1%) during the 4 weeks of the increased rHuEPO dosage. The fourth patient was a 50-year-old man with prepyloric ulcer with stigmata and no active bleeding; his hemoglobin level on admission was RECOMBINANT HUMAN ERYTHROPOIETIN FOR JEHOVAH’S WITNESSES Ball and Winstead 1387 4.3 g/dl.13 On admission to the intensive care unit, his hemoglobin had dropped to 3.5 g/dl, and subcutaneous rHuEPO 20,000 units (250 units/kg) every other day was started. His condition declined, and ultimately he received 5 units of hemoglobin-based oxygen carriers based on compassionate administration. On hospital day 3, his dosage of subcutaneous rHuEPO was increased to 40,000 units/day (500 units/kg/day). Over the next 30 days, the patient’s hemoglobin level increased to a maximum of 7.6 g/dl (absolute change of 4.1 g/dl) before he died from sepsis. These patients with gastrointestinal hemorrhage had the poorest outcomes compared with the other critically ill Jehovah’s Witnesses. One died after receiving both rHuEPO and an hemoglobinbased oxygen carrier; another survived but remained in a vegetative state. In these reports, less aggressive dosing strategies were used, and the subcutaneous route of administration was used in three of the four patients. Starting dosages varied from 50 units/kg/day to 250 units/kg every other day; typically, dosages required upward titration to a maximum of 500 units/kg/day. Furthermore, all patients with gastrointestinal hemorrhage received rHuEPO therapy for extended periods to achieve the desired response; in two, the treatment duration was 30 days or longer. Adjunctive Therapy with Iron, Folic Acid, and Vitamin B12 In most of the case reports, patients received adjunctive therapies along with rHuEPO to enhance production of red blood cells. These therapies included iron, folic acid, and vitamin B 12 (cyanacobalamin). Iron was the most commonly used of the three adjuvant therapies. Iron is used in hemoglobin production, and hemoglobin response to rHuEPO may be greater when the two agents are administered concomitantly. During rHuEPO therapy, functional iron deficiency may be seen, probably due to the inability to adequately mobilize iron stores during the period of enhanced erythropoiesis. The manufacturer recommends that iron stores be evaluated before rHuEPO is administered,14 but this usually is impractical in urgent situations as well as in critical illness. The manufacturer also recommends that all patients receiving rHuEPO after surgery receive supplementation with iron, and notes that virtually all patients receiving rHuEPO eventually require iron supplementation.14 Folic acid and vitamin B12 are used in purine and pyrimidine biosynthesis, which ultimately leads to DNA biosynthesis. When either folic acid or vitamin B 12 is deficient, synthesis of proteins and redirection of metabolic pathways are decreased, which ultimately leads to ineffective erythropoiesis. It is recommended that at least 3–5 µg/day of vitamin B12 should be obtained from meat or dairy products each day.15 Although humans have stores of folic acid, these are readily used, and humans require 50 µg/day from their diet. During critical illness, these dietary needs are generally not met, and supplementation is required. Alternative Therapy with Hemoglobin-Based Oxygen Carriers and Perfluorocarbons Hemoglobin-based oxygen carriers (e.g., PolyHeme; Northfield Laboratories Inc., Evanston, IL) as a substitute for red blood cell transfusions are in clinical development. 16 Although these agents are not currently available for use in the United States, they may be a viable treatment alternative in the future for Jehovah’s Witnesses. These products offer the advantages of no cross-matching required before transfusion, longer shelf-life than packed red blood cells (often > 1 yr), and enhanced oxygen delivery. Also, the risk of infectious disease transmission is low, and nonrecombinant products undergo extensive purification for sterilization. Potential complications associated with hemoglobin-based oxygen carriers include nephrotoxicity from release of free hemoglobin, hypertension, esophageal dysmotility, and abdominal discomfort. These products may also interfere with laboratory testing assays due to their color. Clinicians should be aware of the possible interference and work closely with the clinical laboratory for alternative methods of laboratory testing if possible. Perfluorocarbons are another class of agents developed for use in oxygen delivery. These agents are made of raw materials and are carbon based with either fluorine or other halogens. Perfluorocarbons dissolve oxygen in proportion to the partial pressure of oxygen. They are not derived from human or animal blood, crossmatching is not required before transfusion, risk of infectious disease transmission is low, and immunogenicity is low. The shelf-life of perfluorocarbons is up to 2 years, which is longer than that of packed red blood cells. Potential PHARMACOTHERAPY Volume 28, Number 11, 2008 1388 Table 1. Summary of Case Reports of Jehovah’s Witnesses Who Received Recombinant Human Erythropoietin Therapy Start versus End of Therapy Age (yrs), Hemoglobin Level Hematocrit Therapy Started Treatment Sex (g/dl) (%) (hospital day) Duration Starting Dosage Trauma 36, F3 4.6 vs NR 14 vs ~40 7 17 days 300 units/kg i.v. q.d. 45, F4 3.2 vs > 8 NR vs NR 7 1 wk 36,000 units over 1 wka 48, M5 6.8 vs 11.3 NR vs NR 1 23 days 4750 units i.v. q.d. (50 units/kg) NR vs NR 12 vs 35 1 30 days 20,000 units i.v. q.o.d. 51, F6 44, F7 3.2 vs 9.8 NR vs NR 2 5 days 600 units/kg q.d.a 67, M2 Burns 52, M8 71, F9 General surgery 55, F10 3 vs 7.9 NR vs NR 2 47 days 48,000 units i.v. q.d. 8 vs 11 7 vs 7 24 vs NR NR vs NR 10 15 4 wks 19 days 300 units/kg i.v. q.d. for 7 days 4000 units s.c. 3 times/wk 2.8 vs 10.4 8 vs 33 2 > 30 days 4.6 vs 10.5 NR vs NR 18 > 2 wks 10,000 units i.v. q.d. + 10,000 units s.c. q.d. (280 units/kg) 5000 units s.c. q.d. (60 units/kg) NR vs NR 14.5 vs 27.1 3 11 days 20,000 units i.v. q.d. 63, M10 4.8 vs 6.2 15 vs 20 15 12 days 50, F12 NR vs NR 10.4 vs 38.5 2 > 30 days 50, M13 3.5 vs 7.6 NR vs NR 1 30 days 4000 units s.c. q.d. (50 units/kg) 10,000 units s.c. 3 times/wk (130 units/kg) 20,000 units s.c. q.o.d. (250 units/kg) 43, M10 Gastrointestinal hemorrhage 66, F11 NR = not reported. a Route of administration not reported. b This dosage was given for 10 days, then the frequency was decreased to every other day for 5 doses. adverse effects are splenomegaly and hepatomegaly, flu-like symptoms (back pain, malaise, flushing, fever), and transient thrombocytopenia (on hospital days 3–4). Recommended Use of Recombinant Human Erythropoietin in Jehovah’s Witnesses Published reports of rHuEPO therapy in Jehovah’s Witnesses experiencing traumatic injury, burns, general surgery, or gastrointestinal hemorrhage are limited to case reports and case series (Table 1).2–13 Although it is impossible to recommend a single dosing regimen that is effective for treatment of hemorrhage in a Jehovah’s Witness during critical illness, these case reports illustrate that the drug is effective. Of note, publication bias occurs for case reports that are only positive. These cases summarize the current pertinent medical literature but do not include any unpublished negative or untoward effects of rHuEPO. Potential adverse effects of rHuEPO include thromboembolic and cardiovascular events, hypertension, headache, and arthralgias. When considering treatment with rHuEPO, clinicians should weigh these potential adverse effects against the potential benefits. Furthermore, although case reports provide the poorest level of evidence from which to draw conclusions and make recommendations, no results from randomized controlled trials have been published regarding rHuEPO therapy for critically ill Jehovah’s Witnesses. The available literature demonstrates the variation in the time of starting rHuEPO therapy, the use of both intravenous and subcutaneous routes of administration, the variable and wide range of doses for starting and continuing rHuEPO therapy, the variable administration of adjunctive agents, and the differences in treatment duration. Proactive, early initiation of rHuEPO therapy may be required to achieve optimal response in Jehovah’s Witnesses given that rHuEPO’s effect RECOMBINANT HUMAN ERYTHROPOIETIN FOR JEHOVAH’S WITNESSES Ball and Winstead 1389 Table 1. (continued) Ending Dosage 150 units/kg s.c. 3 times/wk Same as starting dosage 28,500 units i.v. q.d.b (300 units/kg) 7000 units i.v. q8h 300 units/kg q.d.a Adjunctive Agents Same as starting dosage Iron i.m. Iron, vitamin B12, folic acid Iron 300 mg i.m. b.i.d., vitamin B12 100 µg i.m. q.d. Iron i.v. Hemoglobin-based oxygen carrier p.o., iron i.m. Iron, vitamin B12, folic acid 150 units/kg s.c. 3 times/wk Same as starting dosage Iron 300 mg t.i.d. None 10,000 units s.c. q.d. (140 units/kg) Iron p.o. 5000 units s.c. 3 times/wk (60 units/kg) Iron i.v., vitamin B12, folic acid 6500 units i.v. q.o.d. Iron p.o., folic acid, vitamin B12 s.c. Iron i.v., vitamin B12, folic acid Iron i.v., folic acid Same as starting dosage 20,000 units s.c. 3 times/wk (260 units/kg) 40,000 units s.c. q.d. (500 units/kg) Hemoglobin-based oxygen carrier, iron p.o. on hemoglobin level is delayed. Furthermore, combining rHuEPO with adjunctive agents such as iron, folic acid, and vitamin B 12 may be required to achieve optimal response. There may be a theoretical benefit to using the intravenous route of administration in a few subgroups of patients, such as patients whose conditions are hemodynamically unstable or obese critically ill patients, in whom drug absorption by the subcutaneous route would be more variable. Most of the case reports provided the rHuEPO dosage as weight based (i.e., in units/kilogram). Evidence is conflicting as to whether this is a required method of rHuEPO dosing. Although the original studies evaluating rHuEPO therapy and hemoglobin response used weight-based dosing strategies, subsequent studies have relied on standardized regimens. A weight-based approach also allows clinicians to gauge the intensity of the dosing regimen. The pharmacokinetic properties of rHuEPO indicate a low volume of distribution (0.042– 0.07 L/kg).17 Therefore, one can estimate that the drug should stay within the intravascular space to maintain its effect instead of distributing widely into tissues and fat. One advantage of standardized dosing is that waste is minimized. In addition, several case reports used standardized dosing. Therefore, it seems reasonable to round doses to the nearest vial size (i.e., 20,000 units). Conclusion The case reports we reviewed demonstrate that rHuEPO may have a role in the treatment of critically ill Jehovah’s Witnesses experiencing trauma, burns, gastrointestinal surgery, or gastrointestinal hemorrhage as an alternative to blood product administration. Selection of dosage and evaluation of adverse events remain areas for future investigation. Along with rHuEPO therapy, appropriate supplementation with iron, folic acid, and vitamin B12 should be strongly considered in patients with critical illness. References 1. Dixon JL. Blood: whose choice and whose conscience? New York State J Med 1988;88:463–4. 2. Kulvatunyou N, Heard SO. Care of the injured Jehovah’s Witness patient: case report and review of the literature. J Clin Anesth 2004;16(7):548–53. 3. Koestner JA, Nelson LD, Morris JA Jr, Safcsak K. Use of recombinant human erythropoietin (r-HuEPO) in a Jehovah’s Witness refusing transfusion of blood products: case report. J Trauma 1990;30(11):1406–8. 4. Kraus P, Lipman J. Erythropoietin in a patient following multiple trauma. Anaesthesia 1992;47(11):962–4. 5. Collins SL, Timberlake GA. Severe anemia in the Jehovah’s Witness: case report and discussion. Am J Crit Care 1993;2(3):256–9. 6. Gilcreast DM, Avella P, Camarillo E, Mullane G. Treating severe anemia in a trauma patient who is a Jehovah’s Witness. Crit Care Nurse 2001;21(2):69–72, 75–8, 80–2. 7. Cothren C, Moore EE, Offner PJ, Haenel JB, Johnson JL. Blood substitute and erythropoietin therapy in a severely injured Jehovah’s Witness. N Engl J Med 2002;346(14):1097–8. 8. Boshkov LK, Tredget EE, Janowska-Wieczorek A. Recombinant human erythropoietin for a Jehovah’s Witness with anemia of thermal injury. Am J Hematol 1991;37(1):53–4. 9. Kim D, Slater H, Goldfarb IW, Hammell EJ. Experience with patients with burns who refuse blood transfusion for religious reasons. J Burn Care Rehabil 1993;14(5):541–3. 10. Wolff M, Fandrey J, Hirner A, Jelkmann W. Perioperative use of recombinant human erythropoietin in patients refusing blood transfusions: pathophysiological considerations based on 5 cases. Eur J Haematol 1997;58(3):154–9. 11. Pousada L, Fiorito J, Smyth C. Erythropoietin and anemia of gastrointestinal bleeding in a Jehovah’s Witness [letter]. Ann Intern Med 1990;112(7):552. 12. Walton T, Macon EJ. Erythropoietin use in a Jehovah’s Witness patient. Ann Pharmacother 2002;36(4):729–30. 13. Gannon CJ, Napolitano LM. Severe anemia after gastrointestinal hemorrhage in a Jehovah’s Witness: new treatment strategies. Crit Care Med 2002;30(8):1893–5. 14. Amgen Manufacturing Ltd. Epogen (epoetin alfa) package insert. Thousand Oaks, CA; 2007. 15. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Anemias. Pharmacotherapy: a pathophysiologic 1390 PHARMACOTHERAPY Volume 28, Number 11, 2008 approach, 5th ed. New York: McGraw-Hill, 2005:1729–45. 16. Stollings JL, Oyen LJ. Oxygen therapeutics: oxygen delivery without blood. Pharmacotherapy 2006;26(10):1453–64. 17. McEvoy GK, ed. Epoetin alfa. In: AHFS drug information 2003. Bethesda, MD: American Society of Health-System Pharmacists, 2003:1460. Injury, Int. J. Care Injured 40 (2009) 21–27 Contents lists available at ScienceDirect Injury journal homepage: www.elsevier.com/locate/injury Review The role of erythropoietin in the acute phase of trauma management: Evidence today N.K. Kanakaris a, G. Petsatodis b, B. Chalidis a, N. Manidakis a, G. Kontakis c, P.V. Giannoudis a,* a Academic Department of Trauma & Orthopaedics, Leeds Teaching Hospitals, Leeds, UK University Orthopaedic Department, G.H. ‘‘G. Papanikolaou’’, Thessaloniki, Greece c Department of Trauma & Orthopaedic Surgery, University of Crete, Greece b A R T I C L E I N F O S U M M A R Y Article history: Accepted 5 September 2008 Trauma patients often present in a state of haemorrhagic shock. Blood products remain the gold standard of resuscitation, but allogeneic blood transfusions (ABTs) are associated with several risks. The stimulating effect of recombinant-erythropoietin (EPO-A) on erythropoiesis has raised interest in its administration as an alternative. The existing evidence on the early use of EPO-A in the acute phase of trauma patients management consists of only 14 publications. The level of evidence of these studies and the number of treated patients was not found to be adequate to support its generalised use, despite their favourable results. Its safety profile, the preliminary proofs of its efficacy, and the additional cyto-protective properties of EPO-A strongly encourage further controlled studies assessing its use in the acute setting of initial trauma management. ß 2008 Elsevier Ltd. All rights reserved. Keywords: Erythropoietin EPO Transfusion alternatives Trauma Review Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Trauma in Jehovah’s witnesses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hip fracture trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Experimental studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . * Corresponding author at: Academic Unit, Trauma and Orthopaedic Surgery, Clarendon Wing, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK. Tel.: +44 113 3922750. E-mail address: [email protected] (P.V. Giannoudis). Abbreviations: ABT, allogeneic blood transfusions; BFU-E, burst forming unit erythrocytes; CFU-E, colony forming units erythrocytes; CFU-GEMM, colony forming units granulocytes erythrocyte monocyte/macrophage; EPO-A, recombinant human erythropoietin alpha; FDA, food and drug administration; Hb, haemoglobin; IGF-1, insulin like growth factor-1; MOF, multiple organ failure; RBC, red blood cells; RCT, randomised controlled trial/s; RDW, red cell distribution width; rhEPO, recombinant human erythropoietin; rmSCF, recombinant murine stem cell factor; rmIL-3, recombinant murine interleukin-3; SCF, stem cell factor; SIRS, systemic inflammatory response syndrome; sTfR, serum transferrin receptor; TRALI, transfusion related acute lung injury; UI/kg, units international per kilogram of body weight. 0020–1383/$ – see front matter ß 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.injury.2008.09.006 21 22 23 23 23 24 24 25 25 25 Introduction Contemporary trauma is characterised by a continuous rise in its incidence and diversity. It can be broadly divided into highenergy trauma (i.e. motor vehicle collisions) that represents the first cause of mortality of the young and active part of the population), and low energy (i.e. falls) that affects the frail and rapidly increasing elderly population.82 Despite the evolution in prophylactic measures and the advances in emergency medicine and acute trauma management, the morbidity and mortality burden is huge.8,11,69,72 The care of the trauma patient usually involves major surgery in the first 48 h, together with the need for blood transfusion due to the initial or N.K. Kanakaris et al. / Injury, Int. J. Care Injured 40 (2009) 21–27 22 Table 1 Adverse effects and risks of allogenic blood transfusions (ABT). a/a ABT Risk Reported incidence References 1 2 3 4 5 6 7 8 9 10 11 12 13 Febrile reactions Urticarial reactions Transfusion related acute lung injury: TRALI Haemolytic reaction Viral hepatitis B Viral hepatitis C Human Immunodeficiency Viral infection Anaphylactic shock Fatal haemolytic reaction Bacterial contamination Human T cell lymphocyte virus I/II Impairment of microcirculatory flow Immune suppression: risk for MOF, SIRS 1:17–200 1:33–100 1:2,000–5,000 1:6,000–70,000 1:31,000–250,000 1:103,000–3,100,000 1:420,000 1:500,000 1:600,000 1:100,000–1,000,000 1:1,900,000 N/A N/A 47,57 31,57 26,95 47,57 20,47,48 20,47,48,76 47,62 47,57 47,93 7,76,94 19,20 21,88 21,61,73,93 ABT, allogenic blood transfusion; MOF, multiple organ failure; N/A, not available; SIRS, systemic inflammatory response syndrome; TRALI, transfusion related acute lung injury. intraoperative blood loss and the necessary resuscitation requirements.2,59,75 Haemorrhage is the leading, but not the only, cause of anaemia in injured patients.66,84 It is correlated with bone, visceral and soft-tissue damage, with operative interventions, repetitive excessive blood sampling, gastrointestinal blood loss, and also impaired post-traumatic bone marrow function, and reduced iron availability.39 It is constantly reported that over 60% of multiple trauma patients, and 30–70% of the elderly with a hip fracture are transfused with allogeneic blood during their hospitalisation.3,33,71 Allogeneic blood transfusions (ABTs) are the gold standard in the effort to restore the transport of oxygen to the tissues. The haemoglobin threshold of transfusion ranges between 7 and 10 g/ dl in the literature.36,57,70 However, significant concerns about the adverse effects of ABT (Table 1) have prompted a review of transfusion practice and the search for a safer and more biologically rational treatment of anaemia. Moreover, the number of units transfused has been shown to be an independent predictor of worse clinical outcome.21,25,61,63 Furthermore the scarcity of blood donors, the cost of maintenance of blood banks, and the increase in demand for blood have all been considerable factors questioning the current practice.59,77 Another reason for further studying the alternatives to ABT in the trauma setting is the respect given to the patients’ autonomy according to certain religious beliefs against receiving allogeneic biological products.40,91 Several surgical and anaesthetic techniques have been developed to reduce bleeding (endoscopy, laparoscopy, electric scalpel, minimally invasive osteosynthesis, invasive radiology, hypotensive anaesthesia, intraoperative blood salvage, re-infusion of postoperative drainage). In addition, a number of biological products that reduce blood loss (aprotinin, antifibrinolytics and desmopressin acetate, factor VIIa), and new drugs that stimulate platelet production (recombinant IL-11 and recombinant human thrombopoietin) have been all implicated in the quest of minimise the need for ABT.9,76,85 Recently, blood substitutes have also been studied in the trauma population such as polymerised human haemoglobin,35,96 perfluorocarbons,83,89 and finally the stimulation of the endogenous production of red blood cells with exogenous erythropoietin therapy. Erythropoietin is a glycoprotein hormone that is secreted predominantly by renal cortical interstitial cells in response to tissue hypoxia and decreased red blood cell mass.68 It has a molecular weight of 30,400 and its responsible gene is located on chromosome 7. Erythropoietin acts directly on the red blood cell precursors in the bone marrow, affecting their proliferation, differentiation and the erythrocyte maturation (Fig. 1). Recently, additional properties have been elicited. The identification of erythropoietin receptors and its autocrine/paracrine production in other organs (brain – astrocytes, neurons, brain capillaries –, spinal cord, retina and testis), the ability of exogenous EPO-A to cross the blood–brain barrier under certain circumstances, and the growing evidence for its neuroprotective and neurotrophic role against various types of neuronal damage (focal ischaemic stroke, concussive brain injury, seizures, autoimmune encephalomyelitis, spinal cord injury) increase the potentials of EPO-A administration.10,12,28,50,98 Recombinant human erythropoietin (rhEPO) has been produced commercially since the mid-1980s by using the ovarian cells of Chinese hamsters, into which the gene for human erythropoietin has been inserted.54 It has an identical sequence to endogenous human erythropoietin and its haematopoietic properties are indistinguishable. Four types of recombinant human erythropoietin exist: alpha, beta, delta and omega, with different pharmacokinetic and pharmacodynamic properties.86 Recombinant human erythropoietin alpha (EPO-A) has been used to stimulate erythropoiesis. Usually, 72 h are required for a significant reticulocyte response in peripheral blood and 10–14 days for an increase in haemoglobin levels. The magnitude of the erythropoietic stimulation by epoetin alfa has been proven to be dose dependent, and has been used in either daily dosing schemes of 300 UI/kg or weekly doses of 600 UI/kg subcutaneously. Since 1989 and its first FDA-approved indication for renal failure anaemia, it has been used in treating anaemias of various a etiologies.22,37,56,64 Furthermore, the evidence for its use during the prolonged hospital stay of the trauma patients, especially in the intensive care setting, is increasingly supportive.15,16,55,81,93 On the other hand, blood loss or post-injury anaemia at the acute setting needs a fast intervention in order to avoid cardiovascular strain and circulatory shock. Thus, EPO-A has not been tried in initial trauma management, but mostly as a preoperative adjuvant to elective surgery.1,24,46,51,60 The aim of this study is to comprehensively review the existing evidence for the use of erythropoietin in the initial stages of trauma management. Materials and methods A standard Medline literature search was performed. The keywords ‘‘erythropoietin’’, ‘‘EPO’’, and ‘‘trauma’’ or ‘‘injury’’ were used in an OVID search engine query (http://gateway.uk.ovid.com, accessed last 15-07-08). As exclusion criteria we used studies referring to elective cases, or to the use of erythropoietin in intensive care or during prolonged hospital stay of trauma cases, or for other types of anaemia besides post-traumatic or intraoperative due to bleeding, review articles, letters to the editor, expert opinion articles, and editorials. Articles’ abstracts were retrieved N.K. Kanakaris et al. / Injury, Int. J. Care Injured 40 (2009) 21–27 23 Figure 1. Erythropoietin interaction on the red blood cell precursors in the bone marrow, affecting their proliferation, differentiation and the erythrocyte maturation. and evaluated for their suitability for review. When the publications included relevant data from previous studies, the original studies were also retrieved and used for the present analysis. Results The initial PubMed query found 771 publications from 1963 till 2008. After applying the exclusion criteria, and evaluating the abstracts of 105 publications, 14 original studies met the inclusion criteria (Table 2). There were 8 studies referring to trauma in Jehovah’s witnesses,13,18,29,43,49,52,53,92 4 prospective/retrospective trials focused on hip fractures,27,32,41,74 and 2 experimental in vivo studies.38,44 literature.13,18,29,43,49,52,53,92 The reported types of trauma were either blunt or penetrating, and in several cases the severity of blood loss reached critical levels. Alternatives means of restoring the lost blood cell volume are limited in these patients, and the option of EPO-A together with iron supplementation offered accelerated erythropoiesis and minimised the time period of these patients being at risk. The administered subcutaneous doses of EPO-A varied between 300 UI/kg three times per week, or daily for 5 consecutive days, or 50 UI/kg every alternate day in a paediatric case.18 The positive results of these case reports have been quoted in the literature by several authors in order to provide arguments towards an expansion of rhEPO indications in the trauma field, despite the fact they are just sporadic reports at a minimal evidence level. Trauma in Jehovah’s witnesses Hip fracture trauma Recombinant human erythropoietin administration in Jehovah’s witnesses refusing blood transfusions has offered a safe and reliable solution in all the case reports we retrieved in the existing The combined administration of intravenous iron and recombinant human erythropoietin (rhEPO or EPO-A) in the Table 2 Studies referring to the use of erythropoietin in the acute trauma setting. a/a Studies Level of evidence5 Number of cases/controls Subject 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Jim43 Koestner et al.49 Kraus and Lipman52 Collins and Timberlake13 Victorino and Wisner92 Gilcreast et al.29 Lanthaler et al.53 Digieri18 Goodnough and Merkel32 Schmidt et al.74 Garcia-Erce27 Izuel-Rami et al.41 Hoynck van Papendrecht et al.38 Jones et al.44 IV IV IV IV IV IV IV IV III–IV III–IV II III II II 1 1 1 1 1 1 1 1 9 4 83 63 15 15 Jehovah’s witness case report Jehovah’s witness case report Jehovah’s witness case report Jehovah’s witness case report Jehovah’s witness retrospective case series Jehovah’s witness case report Jehovah’s witness case report Jehovah’s witness case report Hip fractures prospective case series study Hip fractures prospective case series study Hip fractures prospective case control study Hip fractures retrospective case control study Blood loss in rats experimental in vivo study Blood loss in mice experimental in vivo study a b c Control group treated without iron or EPO-A. Control group treated without any supplement or with only oral iron. Control group treated with iv and oral iron supplementation. vs. vs. vs. vs. 41a 196b vs. 68c 30 45 24 N.K. Kanakaris et al. / Injury, Int. J. Care Injured 40 (2009) 21–27 acute setting of hip fracture surgery was studied by Goodnough and Merkel.32 In their case series they included 7 patients with an intertrochanteric and 2 with a neck of femur fracture, a median age of 78 years (71–90), a median admission haematocrit of 35.2% (42.6–41%), and median intraoperative blood loss of 550 ml (150–1000 ml). They received 150 UI/kg of subcutaneous EPO-A daily until discharge (median length of stay was 6 days/range 3–7). The median net calculated increase in RBC volume after EPO-A administration ranged from 316 to 492 ml (median 398). However, 3 of these 9 patients did not avoid an ABT. The authors refer to a historic control group of hip fractures where ABT was used in 61% of the patients, to conclude in favour of the use of erythropoietin in the hip fracture population, as it decreased the transfusion incidence by half. The lack of a proper control group and the small numbers in the study population certainly limits the strength of evidence of this particular study, and weakens the strength of the authors’ arguments. A similar small series of hip fracture patients treated with rhEPO (150 UI/(kg day) sc plus a single dose of iv iron on the day of admission) have been reported as preliminary results in a review article by Schmidt et al. in 1998.74 In a preliminary analysis of these results the authors reported a steady increase in the reticulocyte count starting from day 1 to day 5, in 3 out of 4 patients, suggesting a favourable effect of EPO-A as an early stimulus of erythropoiesis in hip trauma. In 2005 a prospective, observational, non-randomised study was published addressing more systematically the administration of EPO-A in the same trauma population. Garcia-Erce et al.27 studied the effect of a single subcutaneous dose of 40,000 UI of EPO-A together with three doses of intravenous iron in 75 osteoporotic hip fracture patients with an admissionHb < 13 g/dl. They compared the ABT incidence and the number of transfused blood units together with several clinical outcome measures between this study group and a control group of similarly injured patients, with comparable demographics and treatment methods. The transfusion data showed a significant decrease in the rates of ABT in the EPO-A group that reached statistical significance, especially in female patients and for intertrochanteric hip fractures. Moreover, a trend towards fewer post-operative infections and lower 30-day mortality was observed at the EPO-A group. The accelerated erythropoiesis of the EPO-A group was verified through laboratory tests at the 7th post-surgery day with an increase of the reticulocyte count, serum transferrin receptors (sTfR), and red cell distribution width (RDW). The authors found a clear benefit of using rhEPO in order to reduce the requirements of ABT and the potential adverse effects of allogeneic transfusions in the specific trauma population of hip fractures. The same year another publication focused again on hip fractures and the use of rhEPO.41 The authors studied the effectiveness of perioperative anaemia treatment with iron or a combination of EPO-A and iron, on transfusion rates, postoperative haemoglobin levels, post-operative length of stay, and infection rates. They reviewed retrospectively studied 329 hip fracture patients of whom the EPO-A group (one subcutaneous dose of 40,000 UI) consisted of 63 cases. This subgroup of patients was transfused less than the rest (36.5% vs. 52.0% in the control group with just oral iron supplementation, and 67.6% in the third group of both iv and oral iron administration) (p = 0.002). There were no significant differences in the infection rates and mean post-operative stay between the subgroups. They argued with Goodnough and Merkel,32 Schmidt et al.,74 and Garcia-Erce et al.27 in favour of the combined administration of rhEPO with iv iron in order to minimise ABT. Experimental studies The data produced by the in vivo studies was confirmed in two animal models of acute blood loss. In 1992 Hoynck van Papendrecht et al.38 investigated the hypothesis that the administration of EPO-A can reduce the need for ABT. They produced a rat model of a 20% blood loss and tried different schemes of EPO-A administration starting pre-operatively, or on the day of operation, with a duration of 5 or 10 days, and compared their results with controls which did not receive any EPO-A. Their results indicated that the administration of EPO-A in the acute setting immediately after surgery provided a stimulus for an increase of Hb levels that however did not show the marked difference of the subgroup of early pre-operative EPO-A treatment. The prolonged scheme of EPO-A treatment also offered minimal benefits that appeared after the 8th post-operative day. They concluded that the beneficial effect of EPO-A could be anticipated in elective cases where preoperative administration is feasible but not in the acute setting of traumatic blood loss. Jones et al.44 investigated also the effect of recombinant human erythropoietin (rhEPO) in a mouse model of blood loss (one third of calculated total blood volume). Three study groups received rhEPO and the control group only iron supplementation. In addition to erythropoietin, the authors investigated the effect of two nonerythroid-specific progenitors (recombinant murine stem cell factor (rmSCF) and recombinant murine interleukin-3 (rmIL-3)). The administration of rhEPO in the study groups was initiated 4 days after the blood loss in all groups and consisted of 3 daily doses. The most interesting finding was that the subgroup receiving rhEPO without any other cytokines had a somewhat reduced presence of erythroid progenitors compared to the control. This led the authors to conclude that the response of an individual to the use of rhEPO in the acute setting of trauma is governed by the presence of these rhEPO-target cells. In their model the administration of exogenous erythropoietin did not increase further the numbers of these cells and questioned the rational of supplementing the endogenous erythropoietin secreted after the stimulus of blood loss with rhEPO. Discussion Recombinant human erythropoietin as a blood conservation agent is well established for use in patients with anaemia of a chronic nature (chronic renal failure,78 post-radiation or chemotherapy aplastic anaemia56), or preoperative in elective surgery,23,60 and critically ill patients.14,87 Primarily, the satisfactory safety profile of rhEPO in these clinical settings, and secondarily, the adverse effects of ABTs have lead to an expansion of its use. The reported side effects of EPO-A administration (namely thromboembolic events 10–16%, hypertension, seizures, influenza-like symptoms, etc.—all <10%) originate mostly from the large series referring to elective surgery, critically ill, or patients with chronic anaemia.4,16,67 However, in all of the studies referring to the use of rhEPO in the specific setting of polytrauma (case reports of Jehovah’s witnesses), or low energy hip trauma in the elderly, no major concerns have been raised concerning the safety of the administration of rhEPO. The dosing schemes used varied from single doses of 40,000 UI to daily doses of 150 UI/kg or alternate daily doses of 300 UI/kg. Mostly they were a reflection of the proven safe doses of EPO-A used in the existing large series of erythropoietin in different clinical settings.30,90 The efficacy of exogenous erythropoietin is reported as satisfactory and there appears to be a consensus in the existing trauma literature that it upregulates erythropoiesis and decreases N.K. Kanakaris et al. / Injury, Int. J. Care Injured 40 (2009) 21–27 the transfusion rates and the amount of blood needed per patient.34,57 This effect is seen on standard laboratory tests (reticulocyte cell count) after the 2nd or 3rd day. A few authors also report a correlation of the administration of EPO-A and the resulting blood transfusion decrease with significant clinical outcome parameters such as post-operative infection rates and 30-day mortality.27,41 The supplementary cyto-protective role of EPO-A has been strongly supported by mainly preclinical studies over the last decade and this adds to the arguments in favour of its use in injured patients.12 The results of many animal and a few clinical studies demonstrate that rhEPO protects the brain, spinal cord, retina, heart, and kidney from ischaemic and other types of injury.28,45 Mainly its neuroprotective effect has been proven to minimise tissue necrosis if given in the initial 24 h after blunt brain or spinal trauma.50,98 The large recent RCT of Corwin et al.,16 which included among others 793 trauma patients admitted to intensive care units of 115 medical centres, did not find any significant effect of EPO-A administration on ABT transfusion rates and quantity in comparison to the placebo group. However, the authors reported statistically significant difference in the raise of Hb levels in the EPO-A group (1.6 2 g/dl vs. 1.2 1.8 g/dl), a higher incidence of venous thromboembolism (16.5% vs. 11.5%), and a decrease in the overall mortality rate (8.5% vs. 11.4%). They explained their surprising results regarding the effect of EPO-A on ABT transfusions by the low transfusion threshold (Hb < 8 g/dl) they used and most importantly the decrease on mortality by the cyto-protective properties of EPO-A. The existing evidence from rhEPO administration in the acute setting of the initial management of trauma is nonetheless insufficient. As recorded in this review, it results from just a few studies, which are of low level of evidence. Either they are case reports or small case series, or they are biased due to the lack of proper randomisation. The shortfall of the published studies is mentioned in the existing reviews on the subject.34,58,74 The reported advantages of its use at the small subgroup of injured patients who strongly oppose ABT cannot directly correlate with the clinical conditions of the vast majority of the trauma population. It offers a relatively safe alternative, with unproven efficacy. In injured Jehovah’s witnesses, the supporting evidence does not reach the contemporary requirements of evidence-based medicine. A well-designed and conducted multicentre study is required to provide strong proof of its efficacy in this particular patient group.40,91 The two quoted experimental studies38,44 raise a significant concern regarding the rationale of rhEPO in the acute trauma setting. The basic limitation is the rate and volume of erythropoiesis that is achievable with exogenously administered rhEPO. The available population of cells expressing erythropoietin receptors governs the magnitude of the erythropoietic response anticipated after EPO administration. The cell-targets of EPO are shown in Fig. 1 and are also affected by cytokines (IL3, SCF, IGF-1) besides erythropoietin. The burst forming unit erythrocyte (BFU-E) is the earliest cell of the erythrocyte lineage that can be stimulated by the erythropoietin (endogenous or exogenous), and can act as a threshold to the erythropoietic response besides the administration of rhEPO. The recent addition of the RCT of Corwin et al.16 is a significant step forward that denotes the importance of conducting welldesigned multicentre trials with clear endpoints. Unfortunately it was not focused only in trauma and assessed mostly polytrauma patients who were admitted for over 2 days at an ICU. Another significant parameter is the cost-effectiveness of EPO-A in the trauma population. EPO-A is an expensive drug and its use must be justified by proper health economics analysis. The existing 25 evidence is again drawn from studies referring in other clinical settings.17,79 The conclusion of these studies is mostly in favour of the use of EPO-A and one would expect similar positive results in the acute trauma setting. However, recent studies on critically ill patients failed to identify statistically significant differences with direct financial benefits.16,80 A cost of $2154 for five doses of EPO-A was required to avoid one transfusion. The authors preserved their reservations over its use, and advocated further research focused on the potential clinical and financial benefits in the trauma population. We expect in the near future the publication of randomised controlled trials (RCT) evaluating the safety, efficacy, and costeffectiveness of rhEPO in trauma and polytrauma patients. The necessity of reducing ABT is pressing and stimulates the scientific community towards transfusion alternatives. Of special interest will also be the combination of RBC substitutes and rhEPO therapy, but this should be anticipated in a longer time frame as RBC substitutes are under investigation in phase III trials.42,65,97 A well designed RCT study5,6 should focus on a certain subgroup of trauma or polytrauma (e.g. hip fractures, or pelvic fractures); should include a standardised administration of iv iron and at least two different dosing schemes of EPO-A (e.g. a single dose of 40,000 UI and 150 UI/(kg day)) initiated on admission; should exclude patients with a Hb > 13 g/dl, history of clinically evident venous thromboembolism; should have standardised transfusion trigger thresholds (e.g. Hb < 8.0 g/dl), and include clinical and laboratory endpoints (reticulocyte cell count, Hb, time of recovery of the anaemia, evaluate quality of life and functional recovery of the patient, complication rates, infection rates, length of hospital stay, 30-day mortality rate, etc.). Ideally, these endpoints would be enriched with secondary endpoints (e.g. cognitive function, extent and outcome of brain or spinal necrosis, cardiac functional parameters) assessing the additional cyto-protective effect of EPO-A in blunt head or cardiac trauma patients. The evaluation of erythropoietin’s safety should include blood pressure and venous flow objective measurements. Finally, a power analysis of the necessary study sample in order to have results which reach statistical significance should be performed in order to be successful and be completed at a reasonable time frame. Conclusion The existing evidence doesnot support the administration of recombinant human erythropoietin in trauma patients in the initial phases of their management. There are indications that it has a safe profile at the standard doses of elective cases, and is effective in low energy hip-trauma in the elderly. 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Polyhemoglobin-fibrinogen: a novel oxygen carrier with platelet-like properties in a hemodiluted setting. Artif Cells Blood Substit Immobil Biotechnol 2007;35:481–9. 98. Yazihan N, Uzuner K, Salman B, et al., Erythropoietin improves oxidative stress following spinal cord trauma in rats. Injury, 2008 Jul 15. [Epub ahead of print]. Hematology, June 2006; 11(3): 187–191 The care of a child with multiple trauma and severe anemia who was a Jehovah’s Witness LUCIANA ANDREA DIGIERI, IVAN POLLASTRINI PISTELLI, & CID EDUARDO DE CARVALHO Intensive Care Unit, Pediatric Department, Faculty of Medical Sciences, Santa Casa de São Paulo, Rua Cesário Mota Júnior, 112—CEP 01221-020, São Paulo, Brazil Abstract Jehovah’s Witness followers do not accept blood derived transfusions and available methods for avoiding transfusion have been used with degrees of success, demonstrating that the probability of death after trauma in these patients may not be significantly different from religious groups. In this report, we describe the case of a child victim of a multiple trauma with severe anemia due to blood loss, whose family would not authorize blood transfusion because of their Jehovah’s Witness faith. We discuss the current indications for restricting transfusion, as well as highlighting new tools that contribute to the success of minimizing blood loss, thus avoiding transfusion. Keywords: Blood transfusion, anemia, trauma, Jehovah’s Witness Introduction Trauma is among the main causes of morbidity and mortality in children and adolescents in Brazil and in the United States, contributing a greater number of lost life years than those due to oncologic and cardiovascular diseases added together [1]. Currently, the risks and complications of blood transfusions are being studied and new measures to minimize the need for its use have been developed, in addition to the respect given to the patients’ autonomy or those responsible for their religious beliefs. In this study, we report a case of a child injured by a car accident causing severe anemia, whose family did not authorize blood transfusion because they are Jehovah’s Witnesses, and discuss the current tendency for restricting transfusion, as well as elucidating new tools that contribute to the success of minimizing blood loss, thus avoiding transfusion. Case report Six-year-old male child, coming from São Paulo, was the victim of a motor vehicle accident with transient loss of consciousness at the site of the injury, was transferred by the air transportation unit and taken to the Hospital of the Santa Casa de Misericordia de São Paulo. During transport, the victim received volume expansion (20 ml/kg). The patient arrived immobilized, conscious, oriented, pallor 3 þ /4 þ , respiratory rate of 28 breaths per minute, heart rate of 132 beats per minute, blood pressure of 100/60 mmHg, Glasgow Coma Scale of 15, with scalping, loss of brain matter, cranial depression, periorbirtal edema on the right, abrasion wounds on the face, thorax and abdomen, stable hip, hematoma on the right thigh with femur fracture, a contusion – laceration wound on the left thigh and scrotal region and glans penis hematoma. Initial laboratory investigation revealed a normal amylase, hemoglobin (Hb) of 6 g/dl and hematocrit (Ht) of 18.6%. Volume expansion was repeated using 100 ml/kg of Ringer lactate and the patient was sent for imaging studies (Computerized tomography of the cranium, cervical column, thorax, abdomen and radiography of the entire body), and remained stable with a heart rate between 88 and 110 bpm, respiratory Correspondence: L. A. Digieri, Intensive Care Unit, Pediatric Department, Santa Casa de São Paulo, Faculty of Medical Sciences, Rua Cesário Mota Júnior, 112 –CEP 01221–020– São Paulo, Brazil. Tel: 55 11 5572 2693. Fax: 55 11 55728420. E-mail: [email protected] ISSN 1024-5332 print/ISSN 1607-8454 online q 2006 Informa UK Ltd. DOI: 10.1080/10245330600774942 188 L. A. Digieri et al. rate between 20 and 28 bpm and mean BP between 73 and 83 mmHg. Cranial computed tomography detected brain swelling and cranial depression; the other tomography studies did not reveal other lesions. The radiography study demonstrated a hip fracture and confirmed right femur fracture, and a contrast study ruled out urethral lesion. Despite volume expansion, the patient quickly developed hemodynamic decompensation, with tachycardia and hypotension, and was sent to the surgical department where he received 180 ml/kg of volume, of both colloid and crystalloid, and underwent surgery for cleaning and suture of the scrotal wound and laceration on the left thigh; following these procedures, the neurosurgery team repaired the cranial wound via a right frontal craniotomy of the depressed region and anchoring of the dura mater on the bone border. The plastic surgery team then undertook débridement of the devitalized necrotic tissue and carried out a scalp rotation repair, with approximation of the surgical wound borders. The orthopedic surgery team finalized the operation with reduction and external fixation of the right femur diaphysis fracture through endoscopy. During surgery the patient maintained a normal HR and mean blood pressure on the lower normal limit. Anesthesia was of the duration of 712 h and surgery 7 h. At the beginning of anesthesia the patient presented Ht of 18% and the family would not authorize blood transfusion because their religious faith. Three hours from the beginning of anesthesia, the patient presented an Ht of 14.9% and 5 h from the beginning, an Ht of 12.5%. Blood gas analysis, in series, was done to verify the intraoperative levels of lactate, and all the analyses demonstrated slight compensated metabolic acidosis and slightly elevated lactate (between 1.9 and 3.0). The patient was quickly sent to the Pediatric ICU where he was sedated and intubated. The patient presented pallor 4 þ /4 þ , with miosis and normal pupil reflexes, systolic murmur 2 þ /6 þ present on all auscultation sites of the precordium, heart rate of 124 bpm, BP of 114 £ 47 mmHg, respiratory rate of 15 bpm, Sat O2 of 98%, filiform peripheral pulses with slowed capillary perfusion and filling. The patient presented light metabolic acidosis, 12% Ht, altered coagulation screen, normal electrolytes and renal function. Prophylactic antibiotic therapy was started, as well as vitamin K and erythropoietin therapy (50 UI/kg, SC) on alternate days and folic acid (5 mg) on a daily basis. After a few hours the child developed hypotension, without improvement following volume expansion (60 ml/kg), receiving dopamine at an initial dose of 5 mcg/kg/min, and progressively increasing the dose to 15 mcg/kg/min, establishing hemodynamic improvement. In the 24 h that followed the introduction of dopamine, another three volume expansions were necessary using 20 ml/kg of Ringer lactate due to decreasing BP. Hemodynamic stabilization was only Figure 1. Chronological evolution of mean blood pressure. achieved 48 h after surgery (Figure 1), at which time dopamine infusion was suspended. There was an increase in the Ht from 12 to 14.9 within the period of 1 week. During the postoperative period there was much discussion among the clinical teams regarding blood transfusion despite the family’s non-approval, with the teams in favor of the transfusion arguing that the low Ht levels could damage the area where the scalp was repaired, with loss of the graft and possible meningeal infection. However, the Pediatric ICU team decided that transfusion could be withheld unless anemia decompensated with immediate risk to life, respecting the firm and irrevocable opinion of the family. On the 4th postoperative day, the child developed a fever and after 72 h of clinical and laboratory observation, the antibiotics were changed, and the child returned to a normal apyretic state in 48 h. One week after the trauma, the dose of erythropoietin was increased from 50 to 300 UI/kg on alternating days and intravenous iron hydroxide was introduced at a dose of 3 mg/kg/day during 7 days. Approximately 10 days following the accident, the patient had an Hb of 5.0 d/dl and the scalp showed a central point of necrosis, and again the possibility of transfusion was discussed. One week later, surgical débridement of the necrotic tissue was performed. During the 20 days that the patient stayed at the hospital from the date of the accident, he received 10 doses of erythropoietin. On the 20th day the patient the Hb had increased to 10.3 g/dl (Figure 2), at which time erythropoietin therapy was suspended and a few days later was discharged from the hospital. Figure 2. Chronological evolution of Ht. Severe anemia and Jehovah’s Two months after the accident the patient returned to the hospital for orthopedic follow-up and brought laboratory exams revealing Hb of 12.6 g/dl and Ht of 39.8%. Discussion Jehovah’s Witness, is a religion that has more than 6 million followers worldwide [2], it does not accept blood transfusions due to beliefs based on biblical passages, such as “Every moving thing that liveth shall be meat for you. But flesh with the life thereof, [which is] the blood thereof, shall ye not eat” (Genesis 9: 3 –4) and “And whatsoever man (there be) of the house of Israel, or of the strangers that sojourn among you, that eaten any manner of blood; I will even set my face against that soul that eateth blood, and will cut him off from among his people, for the life of the flesh (is) in the blood” (Leviticus 17:10 –11) [3]. Despite refusing blood derived products, it is known that the probability of death after trauma in previously healthy JW patients is similar to those of other religious groups, usually due to the extra efforts exerted in care because of the refusal of blood, permitting critically lower levels of hemoglobin for longer periods [2]. In general, after bleeding is controlled, the Ht has a tendency to stabilize within 5 –6 days, increasing slowly and progressively from this point on [4]. This observation supports the minimization of transfusion as it is recognized that the initial low Ht level is inevitably followed by recovery. Several publications in the literature describe different Ht levels for the indication of transfusion, most of these with hemoglobin under 8.4. Recently, however, there has been a trend to recommend blood transfusion from either lower values or only in cases of hemodynamic instability, rather than using a specific Ht level as a trigger. Studies have shown that low Ht levels, such as 20%, are well tolerated in healthy and hemodynamically stable children [4] and, therefore, all indications for transfusion should be individually analyzed in order to assure that they are based on the clinical observation of the patient, the presence of eventual hemorrhage and on hemodynamic parameters, rather than the Ht alone. The duty of the blood bank team, hematologists, surgeons, anesthesiologists and intensive care doctors is of fundamental importance for minimizing blood loss, consequently avoiding transfusions. Several surgical and anesthetic techniques have been developed to avoid blood loss, such as the development of approaches that reduce bleeding (endoscopy and laparoscopy); development of the electric scalpel and of biological material, such as “fibrin glues”, that eliminate extensive areas of bleeding; use of new drugs that stimulate platelet production (recombinant IL-11 and recombinant human thrombopoietin), reduce blood loss during surgery (aprotinin, afibrinolytics 189 and desmopressin acetate) and help to reduce acute bleeding (desmopressin and FVIIa); maintain anesthesia with controlled hypotension during surgery (in orthopedic patients it may reduce blood loss up to 50%) and avoid hypothermia (which reduces platelet function and increases bleeding) [5]. However, the most important advance recognized for blood transfusion prevention is the use of recombinant human erythropoietin. Erythropoietin is a glycoprotein that directly acts on the red blood cell precursors in the bone marrow, controlling proliferation, differentiation and erythrocyte maturation. The erythropoietin gene is located on chromosome 7q 11 – 22 and consists of five exons and four introns. Four types of recombinant human erythropoietin exist: alpha, beta, delta and omega and present different pharmacokinetic and pharmacodynamic properties. The administration of recombinant human erythropoietin (alpha) has shown an increase in reticulocyte count and Ht levels, reducing the need for transfusion. Administration can be done subcutaneously, which does not require access and prolongs the increase of serum erythropoietin, sustaining the erythropoiesis stimulus, or can be administered intravenously. The rate of administration can be daily or once, twice or three times a week, according to the necessity of each patient [6]. In JW patients, erythropoietin has been used successfully, avoiding transfusions in several surgical procedures with initial doses of 300 UI/kg, three times a week; other studies have used erythropoietin doses of 150 UI/kg/week for 3 – 4 weeks, prior to elective surgeries, such as thoracic, cardiac or orthopedic, where there can be loss of up to 20% of the total volume, with results demonstrating up to 50% reduction in the need for transfusions. Another form of administration, which is also effective, is with an initial dose of 300 UI/kg/day during five consecutive days, followed by alternating days until a 38% Ht level is achieved. This same study demonstrates a 50% reduction in the number of transfusions a critical anemic patient receives, whether from sepsis, blood loss, reduction in the endogenous erythropoietin production, functional iron deficiency associated to the immune system or frequent exam collection, which are the most important causes of anemia in these patients [7]. Usually, 72 h are required for a significant response in the detection of increased reticulocytes in peripheral blood and 10 – 14 days for an increase in hemoglobin levels [6]. Erythropoiesis is accelerated with administration of erythropoietin and may result in the depletion of the patient iron stock. Therefore, nutritional support and iron supplements are highly recommended during therapy and serum iron should be analyzed on a regular basis [2]. The association of erythropoietin with intravenous iron reduces erythropoietin doses and accelerates the correction of anemia [6,8]. Among 190 L. A. Digieri et al. the possible side effects of erythropoietin use, the literature cites self-limited cold-like conditions, that improves within 24 h with treatment of the symptoms; hypertension and thrombosis associated to the rapid increases in hemoglobin; anaphylactic reaction, hyperkalemia and thrombocytosis, which are rarely reported [6]. Close clinical observation minimizes such occurrences. There are various complications that may be associated to blood transfusion, such as allergic reaction and risk of death associated to mismatched transfusion affecting either ABO, rhesus or other antigen systems. There have also been confirmed reports of bacterial contamination in platelet concentrates and platelets obtained by apheresis affecting 1:2000 units transfused and, even though the prevalence of bacterial sepsis associated to transfusion is unknown, it is estimated that there are 333 – 1000 cases of severe sepsis each year [5]. Furthermore, it is important to bear in mind the transmission of infectious viral diseases through contaminated blood. The rate of HIV transmission is progressively getting smaller from the education and careful selection of the donors; associated with the application of new laboratory tests, such as that which detects the p24 virus antigen and reduces the immune window from 22 to 16 days. This has already become routine in the US blood banks at a cost of 5$ per unit, preventing approximately 8 cases of HIV associated to transfusion per year. The rate of hepatitis C transmission from blood transfusions still remains much higher than that of HIV, and has an incidence of 1:103,000, with 85% of these patients developing chronic hepatitis and 20% developing cirrhosis, with the high risk of hepatocarcinoma [9]. One of the least considered but significant effects of transfusion is immunosuppression which also contributes to mortality [7], several studies have demonstrated that blood transfusions have been associated to higher incidences of postoperative infections in several populations [5,7,10], and greater rates of neoplasia recurrence according to the number of transfusions done [5,9]. One hypothesis that reinforces this connection between transfusion and immunosuppression is the possibility that transfusion may increase the risk for nosocomial infection and sepsis. In a study conducted in Europe, Vincent et al. demonstrated a positive relationship between the increase in transfusion rate and mortality. Mortality was roughly two times greater among patients that received transfusions. After controlling factors such as disease severity and organic failure, the authors estimated that blood transfusions increased mortality in 37%, demonstrating that the mortality rate was significantly greater in the group that received blood in comparison to the group that did not [7]. On average, each unit of transfused blood increased the risk of nosocomial infection by 50%. Patients that receive transfusions are 12 times more susceptible to developing hospital acquired pneumonia [7,11]. Also favoring this theory, there are studies that demonstrate reduced risks of infection and mortality in patients who receive filtered blood. The difference in mortality is mainly due to an increase in the incidence of multiple organ failure (MOF) or anastomosis dehiscence in patients that received non-filtered blood. Other studies demonstrate a significant increase in MOF in victims of trauma who received 6 or more units of blood, reinforcing the hypothesis that the white blood cells of the transfused blood exacerbate an inflammatory response after the trauma [9]. The use of blood lacking leukocytes may result in a shorter period of intensive care and less complications, according to several publications [11]. Bilgin et al. [12] undertook a study comprised of two groups of patients that underwent cardiovascular surgery, with one receiving normal blood and the other receiving blood without leukocytes. It was observed that the group with leukodepletion has a 4% reduction in the mortality rate. Cytokines accumulated during blood storage are not removed during filtration, and therefore reach similar levels in filtered and non-filtered blood [9]. In studies done in critical ICU patients that developed acute respiratory distress syndrome (ARDS) after hospitalization and had analysis to identify risk factors for its development and subsequent mortality, it was demonstrated that blood transfusion significantly increases this risk and death by ARDS, having a dose dependent effect [10]. The risk and adverse effects of blood transfusions has led to the development of blood substitutes. Several components are in varying stages of development and testing, but the side effects are still too great, limiting their use on a routine basis. Polymerized human hemoglobin is being developed and does not seem to present toxicity associated to its components. In two published studies, the patients received up to 6 units of this polymer (equivalent to 6 units of blood) without demonstrating fever, renal toxicity, liver dysfunction or other signs of toxicity. Even though the sample in these studies is small, if the safety and efficacy of this polymerized hemoglobin is to be confirmed in more comprehensive studies, a significant reduction may occur in conventional blood transfusion, especially those done electively [9]. Intraoperative hemodilution may be better tolerated than postoperative anemia because of the reduced need of oxygen during general anesthesia [9]. The only indication for blood transfusion is in increasing oxygen supply for the tissues. The normal response to normovolemic anemia is an increase in cardiac output and O2 extraction in critical ill patients [9]. The technical variation and duration of blood storage may contribute red blood cell deformation, altering O2 Severe anemia and Jehovah’s availability, and reduces 2,3-diphosphoglycerate when stored longer than one week, also reducing O2 liberation to the tissues, increasing hemoglobin affinity for oxygen. Therefore, stored blood may harm tissue consumption of O2 in critical patients [7 –9]. Patients who receive erythropoietin need O2 for shorter periods because there is an increase in 2,3diphosphoglycerate in the erythrocytes that shifts the hemoglobin dissociation curve to the right [8]. It is known that the immunomodulatory effects of transfusion may not be well tolerated in critical patient, where sepsis, trauma, pneumonia and respiratory failure may simulate an initial inflammatory response that is increased by blood derived products. Furthermore, other risks of transfusion such as allergic reactions, infection and hemolysis also increase mortality among patients that receive blood transfusion. Unfortunately, the individual indications for transfusions are often not well defined, and are frequently carried out solely to normalize hemoglobin rates. It is important to define the risks and benefits of blood transfusion and, with the development of new strategies, attempt to avoid unnecessary transfusions and adopt new strategies, such as erythropoietin and iron administration. The experience of the studies done by JW with the development of alternative forms of treatment in relation to blood transfusions may many times be applied without harm and reduce mortality rates. The goal of this case report is to alert doctors about the several inherent risks of blood transfusions and provide alternative tools for treating severe anemia, especially in critically ill children without using blood derived products. Acknowledgements We are grateful to the Support Center for Scientific Publications of Santa Casa de São Paulo — Faculty of Medical Sciences for the editorial assistance. 191 References [1] Robb TV, LaHurd N, Kemp L, Carmel M, Suecoff S, Rubin DH. Impact of adult trauma center certification on pediatric emergency visits. J Emerg Nurs 2004;30:413. [2] Varela JE, Gomez-Marin O, Fleming E, Cohn SM. The risk of death for Jehovah’s Witnesses after major trauma. J Trauma 2003;54:967–972. [3] Nelson BS, Heiskell LE, Cemaj S, O’Callaghan TA, Koller CE. Traumatically injured Jehovah’s Witnesses: A sixteen-year experience of treatment and transfusion dilemmas at a level I trauma center. J Trauma 1995;39:681–685. [4] Shafi S, Gilbert JC, Carden S, Allen JE, Glick PL, Caty MG, Azizkhan RG. Risk of hemorrhage and appropriate use of blood transfusions in pediatric blunt splenic injuries. J Trauma 1997;42:1029 –1032. [5] Shander A. Surgery without blood. Crit Care Med 2003;31:S708–S714. [6] Ng T, Marx G, Littlewood T, Macdougall I. Recombinant erythropoietin in clinical practice. Postgrad Med J 2003;79:367–376. [7] Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, Meier-Hellmann A, Nollet G, Peres-Bota D. Anemia and blood transfusion in critically ill patients. JAMA 2002;288:1499–1507. [8] Silverberg DS, Blum M, Agbaria Z, Deutsch V, Irony M, Schwartz D, Baruch R, Yachnin T, Steinbruch S, Iaina A. The effect of i.v. iron alone or in combination with low-dose erythropoietin in the rapid correction of anemia of chronic renal failure in the predialysis period. Clin Nephrol 2001;55:212–219. [9] Caruso LJ, Gabrielli A. Transfusion therapy in the critically ill. Curr Opin Anaesthesiol 1999;12:149–153. [10] Jackson WL, Jr, Shorr AF. Blood transfusion and the development of acute respiratory distress syndrome: More evidence that blood transfusion in the intensive care unit may not be benign. Crit Care Med 2005;33:1420–1421. [11] Shorr AF, Jackson WL. Transfusion practice and nosocomial infection: Assessing the evidence. Curr Opin Crit Care 2005;11:468–472. [12] Bilgin YM, van de Watering LM, Eijsman L, Versteegh MI, Brand R, van Oers MH, Brand A. Double-blind, randomized controlled trial on the effect of leukocyte-depleted erythrocyte transfusions in cardiac valve surgery. Circulation 2004; 109:2755–2760. Journal of Clinical Anesthesia (2008) 20, 538–541 Case report Management of hemorrhagic shock when blood is not an option Colin F. Mackenzie MB ChB, FRCA (Professor) a,b,⁎, Chet Morrison MD (Assistant Professor)c , Mahmood Jaberi MD (Assistant Professor)d , Thomas Genuit MD (Attending Surgeon)e , Subishani Katamuluwa BS (Research Assistant)a , Aurelio Rodriguez MD (Professor)f a National Study Center for Trauma and Emergency Medical Systems, University of Maryland School of Medicine, Baltimore, MD 21201, USA b Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA c Department of Surgery, Michigan State University, East Lansing, MI 48824, USA d Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA e Department of Surgery, Sinai Hospital, Baltimore, MD 21215, USA f Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA Received 5 June 2007; revised 22 May 2008; accepted 22 May 2008 Keywords: Blood; Blood products; Coagulation; Hemorrhagic shock; Jehovah's Witness patients Abstract Objective: To describe an alternative approach to management of severe life- threatening hemorrhagic shock and the outcome when blood was not a treatment option. Design: Case Report of the use of a Hemoglobin Based Oxygen Carrier (HBOC-201)when control of hemorrhage and intravenous crystalloids were unsuccessful in reversal of hemorrhagic shock and progressive ischemia. Setting: Trauma Center. Patients: Jehovah's Witness. Outcome: Hospital discharge and 6 month follow-up uneventful. © 2008 Elsevier Inc. All rights reserved. 1. Case report A 23 year-old 70.3-kg Jehovah's Witness man was a pedestrian struck by a car and admitted to the trauma center at University of Maryland, Baltimore, MD. He complained of pelvic and abdominal pain and shortness of breath. On examination, blood pressure (BP) was 118/65 mmHg, heart ⁎ Corresponding author. Department of Anesthesiology, University of Maryland, Baltimore, MD 21201, USA. E-mail address: [email protected] (C.F. Mackenzie). 0952-8180/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jclinane.2008.05.012 rate (HR) was 99 bpm, respiratory rate (RR) was 28 breaths per minute, and oxygen saturation (SpO2) was 96% on face mask oxygen. He was noted to have abrasions on his right flank, abdomen, and thorax with tender abdomen and 2+ hematuria. Radiography showed multiple fractures of the right ribs, a small left pneumothorax, fractures of the left iliac wing, left acetabulum, and anterior column, and separation of the symphysis pubis and both sacroiliac joints. He had a grade 3 liver laceration involving the posterior segment of the right hepatic lobe extending into the right hepatic vein and portal system. Active bleeding When blood is not an option 539 Fig. 1 All values of red blood cell and plasma (total) Hb (left y-axis [g/dL]) and Hct (right y-axis [%]) throughout hospitalization of a Jehovah's Witness patient. Arrows = the timing of dosages (Hb [g]) of Hb-based oxygen carrier (HBOC-201; Hemopure; Biopure Corp). Point 1 = Hb and Hct admission values; point 2 = when consent was obtained to administer HBOC-201; point 3 = postadministration values of 150 g of HBOC-201; point 4 = half-life (19 hrs) of HBOC-201; point 5 = 8 days after first administration of HBOC-201, showing intrinsic increases in Hb and Hct values. was noted in the space of Retzius and periurethral region. There was bleeding from both right and left internal iliac arteries and his hepatic artery. His admission hemoglobin (Hb) was 13.4 g/dL and progressively decreased to a nadir of 4.5 g/dL (Fig. 1, point 1 to point 2). Despite infusion of 2,550 mL of crystalloid, 500 mL of hetastarch, and efforts to control bleeding, BP values decreased to 84/44 mmHg, with a HR of 110 bpm for the initial 8 hours. He refused blood transfusion. The patient's trachea was intubated, he was sedated, and his lungs were mechanically ventilated with neuromuscular block to minimize oxygen consumption, because serum lactate was increasing despite efforts at fluid resuscitation (Table 1). A left tube thoracostomy was performed to relieve the pneumothorax. Ninety minutes after admission, he underwent angiographic selective gel foam embolization until hemostasis of the bleeding sites was achieved, in the left and right internal iliac arteries and their subdivisions, and in segmental branches of the right hepatic artery. An inferior vena caval filter was placed. He next underwent percutaneous screw fixation of his sacral disruption, which resulted in good posterior pelvic alignment. Eight hours after this minimal blood loss procedure, his Hb was 6.1 g/dL and his lactate increased from 3.0 to 4.3 mmol/L. The patient was then begun on a course of vitamin K (10 mg), erythropoietin (14,000 U/d for 6 days, then 20,000 U on alternate days), iron supplements (100 mg), and vitamin C (500 mg) to maximize erythropoiesis. Because the patient's trachea was intubated, he was sedated and receiving mechanical ventilation, we obtained consent from the patient's family to use a nonhuman, Hbbased, acellular oxygen-carrying solution (HBOC-201, Hemopure; Biopure Corp, Cambridge, MA). Under a Food and Drug Administration (FDA) compassionate use and institutional review board–approved protocol, 150 g of HBOC-201 was administered on hospital day 2. With HBOC-201 dosing, there was an increase in total Hb (plasma Hb plus Hb in the red cells) from 4.6 to 7.4 g/dL within 24 hours. At this same time, hematocrit (Hct, %) after HBOC201 infusion decreased from 11.7% to 11.6%, indicating volume expansion by the cell-free HBOC-201 (Fig. 1, point 2 to point 3). Increased plasma Hb from HBOC-201 augmented oxygen carriage of the circulating red cells, as judged by the normalization of serum lactate (Table 1). The half-life of HBOC-201 is about 19 hours because total Hb decreases from 7.4 to 5.1 g/dL by hospital day 4 (Fig. 1, points 3 to 4). To maintain efficacy (in this case, Hb concentration), we Table 1 Serum lactate levels after the patient's admission Hours after admission Level (mmol/L) 0 2 7 9 12 17 30 3.0 4.2 4.2 4.3 3.3 2.5 1.9 Total number of hours after admission was 30. 540 administered redosing of 30 g of HBOC-201 on hospital day 5. Total Hb increased from 4.5 to 5.9 g/dL. On hospital day 8, the patient's trachea was extubated. Erythropoiesis was stimulated and Hct increased from 14.2% on hospital day 10 to 21.7% (Fig. 1, point 5 onward). This patient received no blood. His pelvic injuries and acetabulum were repaired by fluoroscopy-directed placement of percutaneous screws on hospital day 12, when his Hct was 26%. On the day after surgery, the patient was discharged home with an Hct value of 25.1% and was walking on crutches. His follow-up has been uneventful for more than 6 months, and he has resumed all his preinjury activities except kick boxing, because of some limitation of left hip movements. 2. Discussion The precipitous decrease of Hb and Hct in the hours after admission to the trauma center, together with his lactate levels increasing to 4.3 mmol/L despite administration of fluids and efforts to control hemorrhage, all indicate that this patient was in uncontrolled hemorrhagic shock. Critical Hb concentration is about 7 g/dL, below which tissue oxygenation is imperiled [1]. Many different approaches have been described in the literature to overcome the physiologic deficit resulting from acute inadequacy of Hb [2] in patients after trauma. Surgical control of bleeding and blood transfusion are considered the standards of care. The approach described in this Jehovah's Witness patient avoided any open surgical procedure, either for hemorrhage control of his liver and vascular injuries or orthopedic stabilization of major pelvic and acetabular fractures. Nonoperative management for liver injuries is less likely to fail than for splenic or renal injury [3]. Percutaneous fixation of sacral injuries diminishes potential blood loss and operative times [4]. Closed reduction and percutaneous fixation of anterior column [5], or both anterior and posterior column acetabular fractures, using cannulated screws and fluoroscopy, reduce blood loss and operative time. Mean blood loss for these procedures can be less than 100 mL [6]. A problem associated with erythropoiesis after trauma is that there is inadequate erythropoietin response [7] because of release of inflammatory cytokines that down-regulate the erythropoietin gene, inhibit bone marrow, and alter iron metabolism [8]. Erythropoietin levels are preserved so that the persistent anemia associated with injury is related to failure of the bone marrow to respond to erythropoietin. In one study of human bone marrow taken from patients after trauma, addition of exogenous erythropoietin not only failed to increase hematopoietic progenitor colony counts but appeared to have a dose-dependent suppressive effect [7]. These data call into question the benefit of administration of recombinant erythropoietin for trauma patients to improve hematopoiesis. Even when benefit is shown, erythropoietin effects take 10 days to three weeks [9,10]. C.F. Mackenzie et al. However, in this patient, until alternative strategies were worked out and to obtain FDA compassionate use approval, erythropoietin was started. One intervention that can promote a more balanced proinflammatory and antiinflammatory response, and may reduce posttraumatic complications, is hypertonic saline (NaCl) [11]. After a single dose of 250 mL of 7.5% NaCl and 6% dextran 70, neutrophil activation was blunted and monocyte redistribution was altered to minimize the decreased production of myeloid colony-stimulating cytokines after multiple injuries [11,12], and proregulatory cytokines were increased. Such an immunomodulatory response may reduce posttraumatic complications including multiorgan failure and sepsis. Use of the nonoperative approach to control bleeding from the liver and pelvic injuries was an important method to minimize blood loss. The use of percutaneous screw fixation to stabilize sacroiliac disruption allowed bleeding (which would normally be uncontrolled until definitive reduction of the fracture) to be reduced early in this patient's care, with minimal blood loss and operative time. Acetabular fracture repair is usually delayed until the patient is stabilized; percutaneous repair is used to reduce blood loss, and it produces a good functional outcome [5]. The infusions of HBOC-201 enabled Hb concentration to be maintained and sedation, neuromuscular paralysis, and intubation to be discontinued. Reports in humans suggest that HBOC-201 increases serum iron, ferritin, and erythropoietin, and stimulates erythropoiesis, with a resulting increase in Hct one week later (day 9 in this patient), which is equivalent to one U of blood transfusion after HBOC-201 [13]. In addition, an acellular Hb solution can facilitate microcirculatory oxygen delivery to ischemic tissue, such as that found in uncontrolled hemorrhagic shock [14,15], and can maintain life in trauma patients with cellular Hb values less than three g/dL [16]. Iron, folic acid, and vitamin B12 should be administered, but it is unclear whether erythropoietin is beneficial or detrimental. Blood draws should be minimized. Because reticulocyte counts require a separate blood draw at our institution, none was performed. Pediatric-sized blood tubes were used to minimize the 41 ± 39.7 mL/24-hour volumes usually drawn in critically ill patients [17]. In view of the potential benefit of hypertonic saline over other resuscitative solutions (including blood) in counterbalancing the inflammatory response and decreasing hemodilution, 7.5% NaCl and 6% dextran may be helpful for initial resuscitation and should be considered in patients when blood is not an option. Finally, once stabilization of the patient has occurred, acute normovolemic hemodilution [18,19] is a blood-conserving technique that would be useful if a known high blood loss procedure (eg, a multilevel spinal stabilization procedure) had to be undertaken to provide definitive correction of traumatic injuries. In this patient, hemodilution with HBOC201 would maintain Hb during such surgery until autologous blood reinfusion. The successful outcome in this patient shows that hemorrhagic shock can be managed without When blood is not an option blood, if expeditious angiographic embolization and percutaneous skeletal fixation procedures are used to control bleeding, and repeated dosages of Hb solution are provided until intrinsic Hb increases in about one week. 541 [10] [11] References [12] [1] Intaglietta M. Microcirculatory basis for the design of artificial blood. Microcirculation 1999;6:247-58. [2] Gannon CJ, Napolitano LM. Severe anemia after gastrointestinal hemorrhage in a Jehovah's Witness: new treatment strategies. Crit Care Med 2002;30:1893-5. [3] Velmahos GC, Toutouzas KG, Radin R, Chan L, Demetriades D. Nonoperative treatment of blunt injury to solid abdominal organs: a prospective study. Arch Surg 2003;138:844-51. [4] Nork SE, Jones CB, Harding SP, Mirza SK, Routt ML Jr. Percutaneous stabilization of U-shaped sacral fractures using sacro-iliac screws: technique and early results. J Orthop Trauma 2001;15:238-46. [5] Crowl AC, Kahler DM. Closed reduction and percutaneous fixation of anterior column acetabular fractures. Comput Aided Surg 2002;7: 169-78. [6] Parker PJ, Copeland C. Percutaneous fluoroscopic screw fixation of acetabular fractures. Injury 1997;28:597-600. [7] Hobisch-Hagen P, Wiedermann F, Mayr A, et al. Blunted erythropoietic response to anemia in multiply traumatized patients. Crit Care Med 2001;29:743-7. [8] Livingston DH, Anjaria D, Wu J, et al. Bone marrow failure following severe injury in humans. Ann Surg 2003;238:748-53. [9] Gabriel A, Kozek S, Chiari A, et al. High-dose recombinant human erythropoietin stimulates reticulocyte production in patients [13] [14] [15] [16] [17] [18] [19] with multiple organ dysfunction syndrome. J Trauma 1998;44: 361-7. van Iperen CE, Gaillard CA, Kraaijenhagen RJ, Braam BG, Marx JJ, van de Wiel A. Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients. Crit Care Med 2000;28:2773-8. Rizoli SB, Rhind SG, Shek PN, et al. The immunomodulatory effects of hypertonic saline resuscitation in patients sustaining traumatic hemorrhagic shock: a randomized, controlled, double-blinded trial. Ann Surg 2006;243:47-57. Moore FA, Peterson VM, Moore EE, Rundus C, Poggetti R. Inadequate granulopoiesis after major torso trauma: a hematopoietic regulatory paradox. Surgery 1990;108:667-75. Hughes GS, Francom SF, Antal EJ, et al. Hematological effects of a novel hemoglobin based oxygen carrier in normal male and female subjects. J Lab Clin Med 1995;126:444-51. Page TC, Light WR, McKay CB, Hellums JD. Oxygen transport by erythrocyte/hemoglobin solution mixtures in an in vitro capillary as a model of hemoglobin-based oxygen carrier performance. Microvasc Res 1998;55:54-64. York GB, Eggers JS, Smith DL, et al. Low-volume resuscitation with a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhage. J Trauma 2003;55:873-85. Gould SA, Moore EE, Hoyt DB, et al. The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable. J Am Coll Surg 2002;195:445-52. Vincent JL, Baron JF, Reinhart K, et al. Anemia and blood transfusion in critically ill patients. JAMA 2002;288:1499-507. Weiskopf RB, Viele MK, Feiner J, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998; 279:217-21. Monk TG, Goodnough LT. Acute normovolemic hemodilution. Clin Orthop Relat Res 1998(357):74-81. Case Reports Care of the Injured Jehovah’s Witness Patient: Case Report and Review of the Literature Narong Kulvatunyou, MD,* Stephen O. Heard, MD† Department of Surgery, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; and Department of Anesthesiology and Department of Surgery, UMass Memorial Medical Center, Worcester, MA Care for the Jehovah’s Witness patient can be a challenge and often a dilemma to clinicians because of the patient’s religious beliefs and teachings against receiving blood and blood products, especially in emergency or trauma settings. We present a case of a severely injured elderly Jehovah’s Witness patient who survived. We also review the literature and offer an organized approach to care for such patients. © 2004 by Elsevier Inc. Keywords: Anemia; blood transfusion; erythropoietin; Jehovah’s Witness patients; trauma. Introduction Over one million Jehovah’s Witnesses live in the Unites States.1 Their religious conviction against receiving blood and blood products can create a difficult clinical dilemma, particularly in the trauma setting. Improvements in surgical technique, decreased phlebotomy rates, and use of erythropoietin have allowed clinicians to perform quite complex surgical procedures such as coronary artery bypass grafting2 or liver transplantation.3 However, in an acute emergency with a significant amount of blood loss, awareness and preparation are key elements to limit further blood loss and improve the chances of patient survival. We present a case of a severely injured Jehovah’s Witness patient, review the literature, and offer an organized approach to care for such patients. *Attending Surgeon and Surgical Intensivist, Ramathibodi Hospital †Professor and Chairman of Anesthesiology, UMass Memorial Medical Center E-mail: [email protected] Address correspondence to Dr. Heard at the Department of Anesthesiology, UMass Memorial Medical Center, 55 Lake Ave. North, Worcester, MA 01655, USA. Received for publication August 21, 2003; revised manuscript accepted for publication February 2, 2004. Journal of Clinical Anesthesia 16:548 –553, 2004 © 2004 Elsevier Inc. All rights reserved. 360 Park Avenue, South, New York, NY 10010 Case Reports A 67-year-old man was an unrestrained driver in a car that hit a tree. He reported no loss of consciousness and was hemodynamically stable at the scene. He was admitted to an emergency room at an outside hospital, at which time a hematocrit (Hct) level of 36.4% was noted. After an episode of hemoglobin (Hb) desaturation, he was transferred to UMass Memorial Medical Center. In the Emergency Department of this institution, he became transiently hypotensive (blood pressure 80 mmHg) but responded promptly to an intravenous (IV) crystalloid bolus. The only active external bleeding source was the nose, which was easily controlled. The remainder of the work-up revealed right-sided rib fractures, right anterior chest wall and mediastinal hematomas, left pneumothorax, bilateral pulmonary contusions, and fractures of the left distal humerus and left distal femur. The admitting Hb level was 9.7 g/dL. Although a left chest tube 0952-8180/04/$–see front matter doi:10.1016/j.jclinane.2004.02.002 Care of Jehovah’s Witness patients: Kulvatunyou and Heard Figure 1. Hemoglobin concentration (gm/dL; solid squares) or reticulocyte count (%, open circles) as a function of hospital day. E ⫽ doses of erythropoietin (48,000 units); arrow ⫽ daily doses. was inserted, the patient’s respiratory status slowly deteriorated, and he required tracheal intubation and mechanical ventilation. Prior to intubation, he stated adamantly that he did not want to receive any blood or blood products. His past medical history was significant for a right hemispheric stroke and a recent open reduction and internal fixation of a left hip fracture. Because the left femur fracture involved the femoral plate, operative management was required, and he was taken to the operating room (OR) for application of an external fixator. His Hct just prior to transfer to the OR was 22.5%. Fluid intake in the emergency room was 5500 mL of normal saline and urine output was 1000 mL. In the OR, 700 mL of lactated Ringer’s solution was administered and the patient’s urine output was 130 mL. Blood loss was 200 mL. Postoperatively, he was admitted to the surgical intensive care unit (ICU) and monitored with a pulmonary artery (PA) catheter that measured cardiac output (CO) and mixed venous oxygen saturation (SvO2) continuously. Over the next 24 hours, he received a total of 7.6 L of crystalloid, 1000 mL of hetastarch, and norepinephrine to maintain adequate end-organ perfusion. Urine output was 1985 mL. Pulmonary capillary wedge pressure ranged from 13 to 16 mmHg. Blood urea nitrogen (BUN) and creatinine were 14 mg/dL and 1.0 mg/dL, respectively. To minimize metabolic demand, mild hypothermia was maintained (35.5°C), and the patient was heavily sedated and paralyzed. On hospital day #2, his hemodynamic status stabilized and the norepinephrine was discontinued. His Hb had decreased to 3 g/dL (Figure 1). Therapy with iron, folate, vitamins B12 and K, and erythropoietin (48,000 units IV daily; Ortho-Biotech, Chapel Hill, NC) was instituted. Blood work was kept to a minimum, with phlebotomy performed every other day and the use of a microcapillary blood gas analyzer (Instrumentation Laboratory, Lexington, MA), which required less than 0.5 mL of blood for electrolyte, arterial blood gas (ABG), and Hct analyses. His arterial oxygen tension (PaO2) was maintained at 150 Figure 2. Oxygen delivery (mL/min 䡠 M2; solid squares) or consumption (mL/min 䡠 M2; open circles) during the first 8 days of hospitalization. to 200 mmHg. His cardiac index (CI) was always above 3 L/min 䡠 M2 and SvO2 ranged from 38% to 45% (Figure 2). Maximal reticulocyte count was 14% (Figure 1). His ICU course over the next few weeks was complicated by respiratory failure due to his pulmonary contusions and ventilator-associated pneumonia. A percutaneous tracheostomy was performed and he was transferred to a respiratory ICU on hospital day #26, and then to a long-term rehabilitation center on hospital day #47. His discharge Hb level was 7.9 g/dL. Discussion The medical literature was reviewed for trauma cases involving Jehovah’s Witness patients.4-10 Table 1 summarizes these cases and includes severity of injury, lowest Hb levels reported, and outcome. Only those cases in which Hb and outcome were documented and no allogeneic blood or cell saver blood was transfused, are included in the table. We believe our case represents the most severely injured Jehovah’s Witness trauma patient with respect to age, severity of injury (ISS of 29), and Hb level who has survived. The decrease in Hb in our patient was most likely a result of bleeding at the sites of the left femur fracture and rib fractures, epistaxis, pulmonary contusions, and hemodilution (as a consequence of crystalloid resuscitation). In contrast to our case, Rupp et al.7 and Finfer et al.8 described patients with lower Hb levels and comparable injury severity who survived; however, those patients were relatively young. Nelson et al.10 reported their experience treating 77 Jehovah’s Witness trauma patients, including children, but they did not provide descriptions of individual patient injury, severity of injury, management, or outcome. Several strategies can be utilized to treat the Jehovah’s Witness patient, including intraoperative blood salvage, minimizing metabolic demand, maximizing oxygen delivery, reducing iatrogenic blood loss, and increasing red blood cell production. J. Clin. Anesth., vol. 16, November 2004 549 Case Reports Table 1. Summary of Trauma Cases Involving Jehovah’s Witnesses Age/Injury 1.) 17-year-old male: contact sport with ruptured spleen4 2.) 47-year-old male: airplane crash with multiple long bone fracture5 3.) 18-year-old male hemophiliac: motor vehicle crash with splenic laceration6 4.) 18-year-old male: bicycle - car crash with multiple lower extremity and pelvic fractures7 5.) 29-year-old male: motor vehicle crash with multiple long bone fractures8 6.) 30-year-old male: motor vehicle crash with multiple long bone fractures8 7.) 37-year-old male: motor vehicle crash with hemothorax and pelvic fracture9 8.) 44-year-old female: motor vehicle crash with subarachnoid hemorrhage, orbital tripod fracture, facial lacerations, pulmonary contusions, 3 rib fractures, and a grade I splenic laceration24 9.) 24-year-old male: 30-foot fall from window with fractures of right frontal bone, maxilla (Le Fort III), mandible, ribs (right 3–5), left patella and right radial head38 10.) 45-year-old female: train crash with multiple bilateral rib fractures, left hemopneumothorax, contused left lung, and ruptured spleen39 11.) 61-year-old male: fell 30 feet at a construction site with a subdural hematoma, left subarachnoid hemorrhage and fractures of the left scapula, right radius and left ribs40 12.) 39-year-old female: motor vehicle crash with mesenteric hematoma and fractures of the pelvis, lumbar spine, ribs, scapula and elbow40 13.) 43-year-old male: 25-foot fall with dislocated hip and fractures of the acetabulum, humerus, and radius40 14.) 80-year-old female: motor vehicle crash with blunt chest trauma, multiple extremity fractures, and head injury10 15.) 26-year-old male: diving accident with head injury and C-5 fracture with quadraplegia with subsequent GI hemorrhage10 16.) 15-year-old male: gunshot wound to groin with bladder and bowel injuries10 17.) 67-year-old male: motor vehicle crash with pulmonary contusions and left humerus and femur fractures ISS/RTS Hb g/dL ICU LOS (d) Outcome N/A N/A 0 Survived 16 2.6 18 Survived N/A N/A 0 Survived N/A 2.5 N/A 17/7.84 1.6 4 Survived N/A 0.9 0 Cardiac arrest during surgery N/A 4.5 N/A Survived, 42 d hospitalization N/A 3.2 N/A Survived, 19 days hospitalization [blood substitute given] N/A 1.8 1 N/A 3.2 N/A Survived, 24-day hospitalization. N/A 5.4 N/A Survived, 41-day hospitalization N/A 4.0 N/A Survived, 52-day hospitalization N/A 5.7 N/A Survived, 16-day hospitalization N/A 6.5 N/A Death N/A 5.6 N/A Survived N/A 7.9 N/A Survived 29/7.84 3.0 26 Survived, 41 d hospitalization Cardiac arrest Survived, 32-day hospitalization ISS ⫽ injury severity score, RTS ⫽ revised trauma score, Hb ⫽ hemoglobin, ICU ⫽ intensive care unit, LOS ⫽ length of stay in days, N/A ⫽ Not available, GI ⫽ gastrointestinal. 550 J. Clin. Anesth., vol. 16, November 2004 Care of Jehovah’s Witness patients: Kulvatunyou and Heard Perioperative Blood Salvage Use of blood salvage techniques may be accepted by some Witnesses.11 If possible, the use of this modality should be explored before surgery.12 Likewise, autotransfusion of blood retrieved from hemothoraces is also possible.13 Most often, if these techniques are accepted by the patient, a continuous column of blood must be maintained between the salvage device and patient. thermia can have adverse effects on coagulation; thus, the benefits of reducing metabolic rate must be weighed against the risk of inducing a coagulopathy and increasing blood loss.20 Because it is not uncommon for patients to shiver when hypothermia is being induced, neuromuscular block becomes necessary. Use of neuromuscular block can reduce metabolic demand, even without hypothermia. Indeed, some clinicians have reported myocardial ischemia in Jehovah’s Witness patients when paralysis has been reversed prematurely.19 Prevention of Intraoperative Blood Loss A variety of interventions can be utilized to minimize intraoperative blood loss in the OR. Meticulous surgical technique is mandatory. Acute normovolemic hemodilution may be a valuable means to reduce intraoperative blood loss.14 However, an adequate beginning Hct level is required for this technique to be useful and, as mentioned previously, a continuous column of blood must be maintained between the patient and the storage bag. In our patient, Hct was too low at the beginning of surgery for this strategy to be used. Induced hypotension is another technique by which blood loss can be reduced intraoperatively.15 However, this method is often impractical in the trauma patient who is already unstable or hypovolemic, and perhaps underresuscitated. The possible exception is the hypotensive patient who has suffered penetrating torso trauma.16 In such a situation, so-called hypotensive resuscitation (used until definitive control of bleeding in the OR is achieved) may improve patient outcome. Correction of coagulopathies is extremely important and should be dictated by the appropriate laboratory studies; however, most Witness patients will not allow the use of fresh frozen plasma or cryoprecipitate and/or platelets. Pharmacologic aids such as the serine protease inhibitor, aprotinin; lysine analogue antifibrinolytics such as epsilon aminocaproic acid and tranexamic acid; DDAVP; and recombinant human factor VIIa (rhFactor VIIa) may be useful in individual cases.17 However, to date, there have been no controlled trials evaluating the effectiveness of these agents in trauma patients. Nonetheless, there is evidence suggesting that rhFactor VIIa is useful as rescue therapy in patients with exsanguinating hemorrhage.18 Minimizing Oxygen Consumption and Demand Strategies to reduce metabolic demand include sedation, analgesics, neuromuscular blockade, and hypothermia.19 Mechanical ventilation may be useful to prevent hyperventilation and decrease the work of breathing. Whether neuromuscular blockers and/or hypothermia should be used depends on the degree and severity of the physiological insult. The recommended level of hypothermia is 30° to 32°C because oxygen consumption is reduced by almost 50% at these temperatures, with few cardiac side effects.19 Although the oxyhemoglobin dissociation curve is shifted to the left with hypothermia, both the solubility of oxygen in plasma and tissue affinity for oxygen increases. Hypo- Maximizing Oxygen Delivery Oxygen delivery is dependent on Hb concentration, Hb oxygen saturation (SpO2), CI, and, to a lesser extent, the amount of oxygen that is dissolved in plasma. The clinician should strive for SpO2 of 100% and ensure that intravascular volume is optimal. If necessary, an inotropic agent may be used to augment CI once the patient has been volume resuscitated. Although the contribution of oxygen that is dissolved in plasma to overall oxygen delivery is small, increases in oxygen content of slightly greater than 1 volume percent can be achieved by maintaining high PaO2 levels. For those centers that are equipped with hyperbaric chambers, significant increases in oxygen content can be realized with hyperbaric oxygen therapy.21 Artificial blood substitutes (eg, perfluorocarbons) are still being investigated but promise to be of great utility in the future treatment of these patients.22,23 Indeed, there are case reports describing the use of human24 and bovine25 Hb products in Jehovah’s Witness trauma patients. The use of these products is a matter of conscience by the Witness.24 Our patient received a significant volume of crystalloid to maintain intravascular volume. Greater reliance on colloids for resuscitation in this patient may have allowed for smaller volumes of resuscitation fluid to be used. However, large volumes of hetastarch may have adverse effects on coagulation,26 and the use of albumin may be associated with a greater decrease in Hb compared with the use of crystalloid solutions.27 Compared with crystalloid solutions, hypertonic saline solutions (with or without colloids) achieve an efficiency in plasma volume expansion by a factor of 10.28 Definitive evidence that the use of hypertonic saline solutions will reduce tranfusion requirements in trauma patients is lacking. We chose to monitor our patient with a PA catheter that measures CO and SvO2 continuously. In doing so, we were able to assess adequacy of oxygen delivery and estimate oxygen consumption without resorting to phlebotomy. We maintained inspired oxygen concentration (FIO2) at 0.6, thereby achieving a PaO2 in the range of 150 to 200 mmHg, which represented 10% to 12% of the O2 content. Although the oxygen extraction ratio is normally 12% to 20%, it increased to 65% in our patient, indicating a reduction in convective oxygen delivery. However, tissue oxygenation was probably adequate because serial ABGs failed to show the development of a metabolic acidosis indicative of anaerobic metabolism. J. Clin. Anesth., vol. 16, November 2004 551 Case Reports Minimizing Iatrogenic Blood Loss A number of studies have documented that phlebotomy can result in a tremendous amount of blood loss in ICU patients.29,30 Reducing the frequency of testing and the size of the blood sample tube can reduce iatrogenic blood loss.31,32 In addition, point-of-care diagnostic technologies can provide a number of tests that utilize very small amounts of blood.33 Use of noninvasive and invasive oximetric techniques can reduce further the need for blood testing. In addition to the use of continuous pulse oximetry and SvO2, we chose to use a whole blood gas analyzer to measure on a daily basis ABGs, sodium, potassium, ionized calcium, and glucose. Residual blood in the syringe was used to measure Hct in a capillary tube. Less than 1 mL of whole blood was required for these tests. Enhancing Erythropoiesis Increased red blood cell production can be accomplished by administering recombinant human erythropoietin (Procrit or Epogen) and supplemental iron.19 Koestner et al.9 first recommended the use of this agent in trauma patients, and they noted a reticulocyte response varying from 2% to 17%. Two points of interest need to be mentioned. First, it is important to keep in mind that there have been several cases7,19,34-36 in which the authors did not use synthetic erythropoietin despite Hb values as low as 1.4 g/dL and their patients still survived. Some clinicians did not have access to the drug, but the majority omitted it because their patients were young and erythropoiesis was appropriate. Rupp et al.7 noted a reticulocyte count of 24% without using erythropoietin. Because our patient was elderly and his Hb level was 3 g/dL, we chose to use erythropoietin. The reticulocyte count went from 2% to 14%. Second, the clinician must bear in mind that erythropoietin contains small amounts of human albumin (2.5 mg/mL).20,37 Because albumin is a blood product, the subject may require discussion with the patient or patient’s family. Most Jehovah’s Witnesses will accept treatment with erythropoietin. Conclusion We present a case of a severely injured Jehovah’s Witness patient and offer an organized approach to the management of this uniquely ill individual. Hemostasis, minimizing metabolic demand, optimizing oxygen delivery, limitation of iatrogenic blood loss, and use of erythropoietin are the cornerstones of therapy. 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