Diretrizes brasileiras para o manejo de potenciais doadores de órgãos em morte encefálica. Uma força-tarefa composta por Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network e Coordenação Geral do Sistema Nacional de Transplantes

Glauco Adrieno Westphal Caroline Cabral Robinson Alexandre Biasi Cavalcanti Anderson Ricardo Roman Gonçalves Cátia Moreira Guterres Cassiano Teixeira Cinara Stein Cristiano Augusto Franke Daiana Barbosa da Silva Daniela Ferreira Salomão Pontes Diego Silva Leite Nunes Edson Abdala Felipe Dal-Pizzol Fernando Augusto Bozza Flávia Ribeiro Machado Joel de Andrade Luciane Nascimento Cruz Luciano César Pontes Azevedo Miriam Cristine Vahl Machado Regis Goulart Rosa Roberto Ceratti Manfro Rosana Reis Nothen Suzana Margareth Lobo Tatiana Helena Rech Thiago Costa Lisboa Verônica Colpani Maicon Falavigna Sobre os autores

RESUMO

Objetivo:

Fornecer recomendações para nortear o manejo clínico do potencial doador em morte encefálica.

Métodos:

O presente documento foi formulado em dois painéis compostos por uma força tarefa integrada por 27 especialistas de diferentes áreas que responderam a questões dirigidas aos seguintes temas: ventilação mecânica, hemodinâmica, suporte endócrino-metabólico, infecção, temperatura corporal, transfusão sanguínea, e uso de checklists. Os desfechos considerados foram: parada cardíaca, número de órgãos retirados ou transplantados e função/sobrevida dos órgãos transplantados. A qualidade das evidências das recomendações foi avaliada pelo sistema Grading of Recommendations Assessment, Development, and Evaluation.

Resultados:

Foram geradas 19 recomendações a partir do painel de especialistas. Dessas, 7 foram classificadas como fortes, 11 fracas e uma foi considerada boa prática clínica.

Conclusão:

Apesar da concordância entre os membros do painel em relação à maior parte das recomendações, o grau de recomendação é fraco em sua maioria.

Descritores:
Diretrizes; Doação de órgãos; Terapia intensiva; Morte encefálica; GRADE

Abstract

Objective:

To contribute to updating the recommendations for brain-dead potential organ donor management.

Methods:

A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, answered questions related to the following topics were divided into mechanical ventilation, hemodynamics, endocrine-metabolic management, infection, body temperature, blood transfusion, and checklists use. The outcomes considered were cardiac arrests, number of organs removed or transplanted as well as function / survival of transplanted organs. The quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system to classify the recommendations.

Results:

A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong, 11 as weak and 1 was considered a good clinical practice.

Conclusion:

Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak.

Keywords:
Guidelines; Organ donation; Intensive care; Brain death; GRADE

INTRODUÇÃO

O bom andamento do complexo processo de doação de órgãos é essencial para incrementar o pool de órgãos para transplantes, bem como diminuir a crescente desproporção entre o número de pacientes aguardando em lista e a disponibilidade de órgãos.(11 Tullius SG, Rabb H. Improving the supply and quality of deceased-donor organs for transplantation. N Engl J Med. 2018;378(20):1920-9.,22 The Madrid resolution on organ donation and transplantation: national responsibility in meeting the needs of patients, guided by the WHO principles. Transplantation. 2011;91 Suppl 11:S29-31.) Esse processo inclui a identificação do potencial doador, diagnóstico de morte encefálica (ME), acolhimento e entrevista familiar, avaliação da elegibilidade do doador e a manutenção clínica do potencial doador.(22 The Madrid resolution on organ donation and transplantation: national responsibility in meeting the needs of patients, guided by the WHO principles. Transplantation. 2011;91 Suppl 11:S29-31.,33 Dominguez-Gil B, Delmonico FL, Shaheen FA, Matesanz R, O'Connor K, Minina M, et al. The critical pathway for deceased donation: reportable uniformity in the approach to deceased donation. Transpl Int. 2011;24(4):373-8.) Dada a instabilidade clínica observada na ME, estratégias de manejo do potencial doador durante todo o processo são fundamentais para evitar perdas de órgãos e de doadores por parada cardíaca motivadas por falhas de cuidado.(11 Tullius SG, Rabb H. Improving the supply and quality of deceased-donor organs for transplantation. N Engl J Med. 2018;378(20):1920-9.,22 The Madrid resolution on organ donation and transplantation: national responsibility in meeting the needs of patients, guided by the WHO principles. Transplantation. 2011;91 Suppl 11:S29-31.,44 DuBose J, Salim A. Aggressive organ donor management protocol. J Intensive Care Med. 2008;23(6):367-75.,55 Powner D. Aggressive donor care--to what end? J Intensive Care Med. 2008;23(6):409-11.)

As recomendações dessa diretriz têm a finalidade de promover o mínimo de homogeneidade nas condutas, visando contribuir para a atenuação da desproporção entre oferta e necessidade de órgãos para transplantes.

OBJETIVO

Fornecer recomendações para nortear o manejo clínico do potencial doador em ME, visando reduzir a taxa de parada cardíaca do potencial doador e melhorar a viabilidade do enxerto para o transplante.

MÉTODOS

O presente documento atualizou parcialmente as Diretrizes Brasileiras de Manutenção de Órgãos no Potencial Doador Falecido Adulto de 2011.(66 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult): part I. Overview and hemodynamic support. Rev Bras Ter Intensiva. 2011;23(3):255-68.

7 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult): part II. Mechanical ventilation, endocrine metabolic management, hematological and infectious aspects. Rev Bras Ter Intensiva. 2011;23(3):269-82.
-88 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult). Part III: organ-specific recommendations. Rev Bras Ter Intensiva. 2011;23(4):410-25.) A diretriz é direcionada em especial a médicos e profissionais de enfermagem que trabalham em unidades de terapia intensiva (UTIs) de adultos e emergências, envolvidos na assistência de indivíduos adultos com diagnóstico ou suspeita de ME.

As questões clínicas enfatizam medidas de potencial impacto no manejo clínico do potencial doador e foram divididas em: (1) suporte ventilatório; (2) cuidados hemodinâmicos; (3) manejo endócrino e eletrolítico e (4) aspectos específicos que incluem suporte nutricional, infecção e sepse, transfusão de hemácias, controle da temperatura corporal e (5) terapia guiada por metas. Para cada questão foram desenvolvidas perguntas operacionais conforme a metodologia patient-intervention-comparison-outcome (PICO). A população de interesse são potenciais doadores de órgãos em suspeita ou com diagnóstico de ME(33 Dominguez-Gil B, Delmonico FL, Shaheen FA, Matesanz R, O'Connor K, Minina M, et al. The critical pathway for deceased donation: reportable uniformity in the approach to deceased donation. Transpl Int. 2011;24(4):373-8.) e os desfechos considerados para tomada de decisão foram: parada cardíaca, número de órgãos retirados ou transplantados e função ou sobrevida dos órgãos transplantados.

Para cada questão clínica foi conduzida uma revisão sistemática rápida(99 Schünemann HJ, Moja L. Reviews: Rapid! Rapid! Rapid! and systematic. Syst Rev. 2015;4(1):4.,1010 Haby MM, Chapman E, Clark R, Barreto J, Reveiz L, Lavis JN. Designing a rapid response program to support evidence-informed decision-making in the Americas region: using the best available evidence and case studies. Implement Sci. 2016;11(1):117.) das evidências utilizando a seguinte estratégia: (1) Revisão das referências apresentadas nas diretrizes brasileiras(66 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult): part I. Overview and hemodynamic support. Rev Bras Ter Intensiva. 2011;23(3):255-68.

7 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult): part II. Mechanical ventilation, endocrine metabolic management, hematological and infectious aspects. Rev Bras Ter Intensiva. 2011;23(3):269-82.
-88 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult). Part III: organ-specific recommendations. Rev Bras Ter Intensiva. 2011;23(4):410-25.) e da Society of Critical Care Medicine (SCCM)(1111 Kotloff RM, Blosser S, Fulda GJ, Malinoski D, Ahya VN, Angel L, Byrnes MC, DeVita MA, Grissom TE, Halpern SD, Nakagawa TA, Stock PG, Sudan DL, Wood KE, Anillo SJ, Bleck TP, Eidbo EE, Fowler RA, Glazier AK, Gries C, Hasz R, Herr D, Khan A, Landsberg D, Lebovitz DJ, Levine DJ, Mathur M, Naik P, Niemann CU, Nunley DR, O'Connor KJ, Pelletier SJ, Rahman O, Ranjan D, Salim A, Sawyer RG, Shafer T, Sonneti D, Spiro P, Valapour M, Vikraman-Sushama D, Whelan TP; Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Donor Management Task Force. Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med. 2015;43(6):1291-325.) de manutenção do potencial doador de órgãos; (2) Revisão dos tópicos relacionados nas bases de dados DynaMed e UptoDate; (3) Busca no PubMed com ênfase em revisões sistemáticas e ensaios clínicos publicados até janeiro de 2017. A avaliação da qualidade da evidência foi realizada de acordo com o sistema Grading of Recommendations Assessment, Development, and Evaluation (GRADE).(1212 Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ; GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-6.)

As recomendações foram elaboradas e submetidas a dois painéis de discussão presencial realizados em novembro de 2016 e fevereiro de 2017. Para cada recomendação, foi discutida a direção do curso da ação (realizar ou não realizar a ação proposta) e a força da recomendação, definida como forte ou fraca, de acordo com o sistema GRADE.(1212 Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ; GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924-6.) Após o último painel, uma nova revisão sistemática compreendendo os meses de outubro de 2016 a maio de 2020 foi conduzida visando identificar evidências atuais com potencial para modificar as recomendações. Em junho e julho de 2020, foi conduzido um processo Delphi entre os painelistas para revisão da direção e força das recomendações.

RESULTADOS

Foram geradas 19 recomendações, sendo 7 fortes, 11 fracas e uma delas tratada como boa prática clínica. Na tabela 1, apresentamos o resumo das recomendações e na figura 1, o checklist desenvolvido com base nas recomendações para auxiliar no monitoramento de metas clínicas e aplicação das condutas à beira do leito. Uma sugestão para sequência de aplicação das recomendações está apresentada na figura 2.

Tabela 1
Resumo das recomendações
Figura 1
Checklist baseado em evidências para manutenção à beira de leito de potenciais doadores em morte encefálica.

ME - morte encefálica; SaO2 - saturação periférica de oxigênio; FiO2 - fração inspirada de oxigênio; PEEP - pressão expiratória positiva final; Vt - volume total; PAM - pressão arterial média; ΔPp - variação da pressão de pulso respiratória;ΔPAM - variação da pressão arterial média; ΔVS - variação do volume sistólico; PVC - pressão venosa central; Na+ - sódio; K+ - potássio; Mg++ - magnésio; Hb- hemoglobina; NA/ND - não se aplica/não disponível.


Figura 2
Fluxograma para manutenção clínica do potencial doador de órgãos em morte encefálica.

SaO2 - saturação periférica de oxigênio; Vt - volume total; PAM - pressão arterial média; ΔPp - variação da pressão de pulso respiratória; PVC - pressão venosa central; AVP - arginina-vasopressina; DDAVP - 1-deamino-8-D-argininavasopressina; IV - intravenoso.


Recomendações sobre suporte ventilatório

Foram geradas duas recomendações voltadas ao cuidado ventilatório (recomendações 1 e 2 da Tabela 1), com ênfase ao uso da estratégia ventilatória protetora que consiste na associação de volume corrente de 6 a 8mL/kg e positive end-expiratory pressure (PEEP) de 8 a 10cmH2O em potenciais doadores com pulmões normais, além da sugestão de não utilização rotineira de manobras de recrutamento alveolar. Como considerações práticas, adicionamos a possibilidade de associar à estratégia de ventilação protetora, o teste de apneia com pressão positiva contínua (CPAP) para evitar hipoxemia durante o teste, assim como a titulação de fração inspirada de oxigênio (FiO2) e PEEP visando uma saturação periférica de oxigênio (SaO2) > 90% para favorecer a oxigenação dos tecidos.(1313 Mascia L, Zavala E, Bosma K, Pasero D, Decaroli D, Andrews P, Isnardi D, Davi A, Arguis MJ, Berardino M, Ducati A; Brain IT group. High tidal volume is associated with the development of acute lung injury after severe brain injury: an international observational study. Crit Care Med. 2007;35(8):1815-20.

14 Mascia L, Pasero D, Slutsky AS, Arguis MJ, Berardino M, Grasso S, et al. Effect of a lung protective strategy for organ donors on eligibility and availability of lungs for transplantation: a randomized controlled trial. JAMA. 2010;304(23):2620-7.

15 Lebovitz DJ, Reis K, Yun J, Herman L, McCurry KR. An aggressive lung recruitment protocol increases the percentage of lung donors with no increased adverse effect in lung recipients: 3173. Transplantation. 2010;90(2 Suppl):356.

16 Noiseux N, Nguyen BK, Marsolais P, Dupont J, Simard L, Houde I, et al. Pulmonary recruitment protocol for organ donors: a new strategy to improve the rate of lung utilization. Transplant Proc. 2009;41(8):3284-9.

17 Gabbay E, Williams TJ, Griffiths AP, Macfarlane LM, Kotsimbos TC, Esmore DS, et al. Maximizing the utilization of donor organs offered for lung transplantation. Am J Respir Crit Care Med. 1999;160(1):265-71.

18 Gattinoni L, Carlesso E, Brazzi L, Caironi P. Positive end-expiratory pressure. Curr Opin Crit Care. 2010;16(1):39-44.

19 Bezzi MG, Brovia CC, Carballo JM, Elías MI, Moreno AB, Ruiz VR, et al. Impact of implementing a protocol of respiratory care measures and optimization of mechanical ventilation in potential lung donors. Rev Bras Ter Intensiva. 2020;32(4):571-7.

20 Angel LF, Levine DJ, Restrepo MI, Johnson S, Sako E, Carpenter A, et al. Impact of a lung transplantation donor-management protocol on lung donation and recipient outcomes. Am J Respir Crit Care Med. 2006;174(6):710-6.
-2121 Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators, Cavalcanti AB, Suzumura EA, Laranjeira LN, Paisani DM, Damiani LP, Guimarães HP, et al. Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2017;318(14):1335-45.)

Recomendações sobre cuidados hemodinâmicos

Foram geradas três recomendações para orientar os cuidados hemodinâmicos (recomendações 3 a 5 da Tabela 1). Sugere-se a utilização de alíquotas de 30mL/kg de cristaloides em potenciais doadores que se apresentem hipotensos (pressão arterial média - PAM < 65mmHg) e com sinais de fluido-responsividade (aferida preferencialmente com parâmetros dinâmicos), com a finalidade de mitigar a ocorrência de sobrecarga de volume.(2222 Gruenberger T, Steininger R, Sautner T, Mittlböck M, Mühlbacher F. Influence of donor criteria on postoperative graft function after orthotopic liver transplantation. Transpl Int. 1994;7 Suppl 1:S672-4.

23 delaTorre AN, Kuo PC, Plotkin JS, Ridge LA, Howell CD, Bartlett ST, et al. Influence of donor base deficit status on recipient outcomes in liver transplantation. Transplant Proc. 1997;29(1-2):474.

24 Westphal GA, Coll E, de Souza RL, Wagner S, Montemezzo A, Cani de Souza FC, et al. Positive impact of a clinical goal-directed protocol on reducing cardiac arrests during potential brain-dead donor maintenance. Crit Care. 2016;20(1):323.

25 Murugan R, Venkataraman R, Wahed AS, Elder M, Carter M, Madden NJ, Kellum JA; HIDonOR Study Investigators. Preload responsiveness is associated with increased interleukin-6 and lower organ yield from brain-dead donors. Crit Care Med. 2009;37(8):2387-93.

26 Al-Khafaji A, Elder M, Lebovitz DJ, Murugan R, Souter M, Stuart S, et al. Protocolized fluid therapy in brain-dead donors: the multicenter randomized MOnIToR trial. Intensive Care Med. 2015;41(3):418-26.

27 Abdelnour T, Rieke S. Relationship of hormonal resuscitation therapy and central venous pressure on increasing organs for transplant. J Heart Lung Transplant. 2009;28(5):480-5.

28 Minambres E, Coll E, Duerto J, Suberviola B, Mons R, Cifrian JM, et al. Effect of an intensive lung donor-management protocol on lung transplantation outcomes. J Heart Lung Transplant. 2014;33:178-84.

29 Miñambres E, Pérez-Villares JM, Chico-Fernández M, Zabalegui A, Dueñas-Jurado JM, Misis M, et al. Lung donor treatment protocol in brain dead-donors: a multicenter study. J Heart Lung Transplant. 2015;34(6):773-80.

30 Miñambres E, Pérez-Villares JM, Terceros-Almanza L, Dueñas-Jurado JM, Zabalegui A, Misis M, et al. An intensive lung donor treatment protocol does not have negative influence on other grafts: a multicentre study. Eur J Cardiothorac Surg. 2016;49(6):1719-24.

31 Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008;134(1):172-8.

32 Eskesen TG, Wetterslev M, Perner A. Systematic review including re-analyses of 1148 individual data sets of central venous pressure as a predictor of fluid responsiveness. Intensive Care Med. 2016;42(3):324-32.
-3333 Marik PE, Cavallazzi R, Vasu T, Hirani A. Dynamic changes in arterial waveform derived variables and fluid responsiveness in mechanically ventilated patients: a systematic review of the literature. Crit Care Med. 2009;37(9):2642-7.)

Caso o alvo pressórico de PAM ≥ 65mmHg não seja obtido com a expansão volêmica inicial, deve-se iniciar a infusão imediata de noradrenalina para obtenção dessa meta.(3434 Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, et al. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014;40(12):1795-815.

35 Schnuelle P, Lorenz D, Mueller A, Trede M, Van Der Woude FJ. Donor catecholamine use reduces acute allograft rejection and improves graft survival after cadaveric renal transplantation. Kidney Int. 1999;56(2):738-46.

36 Schnuelle P, Berger S, de Boer J, Persijn G, van der Woude FJ. Effects of catecholamine application to brain-dead donors on graft survival in solid organ transplantation. Transplantation. 2001;72(3):455-63.
-3737 von Ziegler F, Helbig S, Kreissl N, Meiser B, Becker A, Kaczmarek I. Norepinephrine versus dopamine pretreatment of potential heart donors - impact on long-term outcome. Ann Transplant. 2013;18:320-6.) O uso da dopamina pode ser considerado nos casos de bradicardia com sinais de baixo débito cardíaco,(66 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult): part I. Overview and hemodynamic support. Rev Bras Ter Intensiva. 2011;23(3):255-68.,3838 Dictus C, Vienenkoetter B, Esmaeilzadeh M, Unterberg A, Ahmadi R. Critical care management of potential organ donors: our current standard. Clin Transplant. 2009;23 Suppl 21:2-9.,3939 Wood KE, Becker BN, McCartney JG, D'Alessandro AM, Coursin DB. Care of the potential organ donor. N Engl J Med. 2004;351(26):2730-9.) mas o seu potencial arritmogênico deve ser considerado.(4040 Rui Q, Jiang Y, Chen M, Zhang N, Yang H, Zhou Y. Dopamine versus norepinephrine in the treatment of cardiogenic shock: A PRISMA-compliant meta-analysis. Medicine (Baltimore). 2017;96(43):e8402.) A administração de baixas doses de dopamina não está recomendada, pois os benefícios na sobrevida do enxerto renal e cardíaco não estão claros e o seu potencial efeito arritmogênico poder aumentar os riscos de parada cardíaca.(4141 Benck U, Hoeger S, Brinkkoetter PT, Gottmann U, Doenmez D, Boesebeck D, et al. Effects of donor pre-treatment with dopamine on survival after heart transplantation: a cohort study of heart transplant recipients nested in a randomized controlled multicenter trial. J Am Coll Cardiol. 2011;58(17):1768-77.

42 Schnuelle P, Gottmann U, Hoeger S, Boesebeck D, Lauchart W, Weiss C, et al. Effects of donor pretreatment with dopamine on graft function after kidney transplantation: a randomized controlled trial. JAMA. 2009;302(10):1067-75.

43 Schnuelle P, Schmitt WH, Weiss C, Habicht A, Renders L, Zeier M, et al. Effects of dopamine donor pretreatment on graft survival after kidney transplantation: a randomized trial. Clin J Am Soc Nephrol. 2017;12(3):493-501.
-4444 Benck U, Jung M, Krüger B, Grimm A, Weiss C, Yard BA, et al. Donor dopamine does not affect liver graft survival: evidence of safety from a randomized controlled trial. Liver Transpl. 2018;24(10):1336-45.)

Recomendações sobre o manejo endócrino e eletrolítico

Manejo endócrino - Na tabela 1 há cinco recomendações referentes ao manejo endócrino, referindo-se ao uso de arginina-vasopressina (AVP), hidrocortisona, desmopressina (DDAVP), hormônios tireoidianos e insulina (recomendações 6, 7, 8, 9 e 10 da Tabela 1, respectivamente). A administração de AVP (bolus inicial de 1 UI seguido da infusão de 0,5 UI/hora a 2,4 UI/hora) e de hidrocortisona (100mg intravenosa de 8/8 horas) nos potenciais doadores em uso de noradrenalina ou dopamina, diminui o requerimento de vasopressores adrenérgicos, tem associação com menor incidência de deterioração cardiovascular e contribui para o controle da poliúria quando há diabetes insipidus.(4545 Follette DM, Rudich SM, Babcock WD. Improved oxygenation and increased lung donor recovery with high-dose steroid administration after brain death. J Heart Lung Transplant. 1998;17(4):423-9.

46 Dhar R, Cotton C, Coleman J, Brockmeier D, Kappel D, Marklin G, et al. Comparison of high- and low-dose corticosteroid regimens for organ donor management. J Crit Care. 2013;28(1):111.e1-7.

47 Jafari R, Aflatoonian R, Falak R, Pourmand G, Dehghani S, Mortazavi M, et al. Down-regulation of inflammatory signaling pathways despite up-regulation of Toll-like receptors; the effects of corticosteroid therapy in brain-dead kidney donors, a double-blind, randomized, controlled trial. Mol Immunol. 2018;94:36-44.

48 Dupuis S, Amiel JA, Desgroseilliers M, Williamson DR, Thiboutot Z, Serri K, et al. Corticosteroids in the management of brain-dead potential organ donors: a systematic review. Br J Anaesth. 2014;113(3):346-59.

49 Pinsard M, Ragot S, Mertes PM, Bleichner JP, Zitouni S, Cook F, et al. Interest of low-dose hydrocortisone therapy during brain-dead organ donor resuscitation: the CORTICOME study. Crit Care. 2014;18(4):R158.

50 Iwai A, Sakano T, Uenishi M, Sugimoto H, Yoshioka T, Sugimoto T. Effects of vasopressin and catecholamines on the maintenance of circulatory stability in brain-dead patients. Transplantation. 1989;48(4):613-7.

51 Kinoshita Y, Yahata K, Yoshioka T, Onishi S, Sugimoto T. Long-term renal preservation after brain death maintained with vasopressin and epinephrine. Transpl Int. 1990;3(1):15-8.

52 Pennefather SH, Bullock RE, Mantle D, Dark JH. Use of low dose arginine vasopressin to support brain-dead organ donors. Transplantation. 1995;59(1):58-62.

53 Plurad DS, Bricker S, Neville A, Bongard F, Putnam B. Arginine vasopressin significantly increases the rate of successful organ procurement in potential donors. Am J Surg. 2012;204(6):856-60; discussion 860-1.

54 Chen JM, Cullinane S, Spanier TB, Artrip JH, John R, Edwards NM, et al. Vasopressin deficiency and pressor hypersensitivity in hemodynamically unstable organ donors. Circulation. 1999;100(19 Suppl):II244-6.
-5555 Katz K, Lawler J, Wax J, O'Connor R, Nadkarni V. Vasopressin pressor effects in critically ill children during evaluation for brain death and organ recovery. Resuscitation. 2000;47(1):33-40.) Arginina-vasopressina e hidrocortisona devem ser iniciadas no mesmo momento em que se inicia a infusão do vasopressor adrenérgico. Desmopressina está indicada para controle da poliúria (diurese > 4mL/kg/hora) em potenciais doadores com diabetes insipidus que mantém a pressão arterial adequada sem vasopressores adrenérgicos. Arginina-vasopressina e DDAVP podem ser associadas em casos refratários.(5656 Benck U, Gottmann U, Hoeger S, Lammert A, Rose D, Boesebeck D, et al. Donor desmopressin is associated with superior graft survival after kidney transplantation. Transplantation. 2011;92(11):1252-8.,5757 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Brand T, Cockfield S, Keshavjee S, Nickerson P, Rao V, Guest C, Young K, Doig C; Pediatric Recommendations Group. Organ donor management in Canada: recommendations of the forum on Medical Management to Optimize Donor Organ Potential. CMAJ. 2006;174(6):S13-32.) Embora a via intra-nasal seja possível, a via preferencial é a intravenosa, em doses de 1 - 2µg a cada 2 a 4 horas,(88 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult). Part III: organ-specific recommendations. Rev Bras Ter Intensiva. 2011;23(4):410-25.,1111 Kotloff RM, Blosser S, Fulda GJ, Malinoski D, Ahya VN, Angel L, Byrnes MC, DeVita MA, Grissom TE, Halpern SD, Nakagawa TA, Stock PG, Sudan DL, Wood KE, Anillo SJ, Bleck TP, Eidbo EE, Fowler RA, Glazier AK, Gries C, Hasz R, Herr D, Khan A, Landsberg D, Lebovitz DJ, Levine DJ, Mathur M, Naik P, Niemann CU, Nunley DR, O'Connor KJ, Pelletier SJ, Rahman O, Ranjan D, Salim A, Sawyer RG, Shafer T, Sonneti D, Spiro P, Valapour M, Vikraman-Sushama D, Whelan TP; Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Donor Management Task Force. Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med. 2015;43(6):1291-325.,1313 Mascia L, Zavala E, Bosma K, Pasero D, Decaroli D, Andrews P, Isnardi D, Davi A, Arguis MJ, Berardino M, Ducati A; Brain IT group. High tidal volume is associated with the development of acute lung injury after severe brain injury: an international observational study. Crit Care Med. 2007;35(8):1815-20.) até obtenção de uma diurese < 4mL/kg/hora.(5656 Benck U, Gottmann U, Hoeger S, Lammert A, Rose D, Boesebeck D, et al. Donor desmopressin is associated with superior graft survival after kidney transplantation. Transplantation. 2011;92(11):1252-8.

57 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Brand T, Cockfield S, Keshavjee S, Nickerson P, Rao V, Guest C, Young K, Doig C; Pediatric Recommendations Group. Organ donor management in Canada: recommendations of the forum on Medical Management to Optimize Donor Organ Potential. CMAJ. 2006;174(6):S13-32.

58 Gramm HJ, Meinhold H, Bickel U, Zimmermann J, von Hammerstein B, Keller F, et al. Acute endocrine failure after brain death? Transplantation. 1992;54(5):851-7.
-5959 Fiser DH, Jimenez JF, Wrape V, Woody R. Diabetes insipidus in children with brain death. Crit Care Med. 1987;15(6):551-3.) Embora a ME esteja associada com queda dos níveis de hormônios tireoidianos, não há evidências que justifiquem sua utilização no potencial doador, mesmo em potenciais doadores com instabilidade hemodinâmica ou função cardíaca comprometida.(6060 Venkateswaran RV, Steeds RP, Quinn DW, Nightingale P, Wilson IC, Mascaro JG, et al. The haemodynamic effects of adjunctive hormone therapy in potential heart donors: a prospective randomized double-blind factorially designed controlled trial. Eur Heart J. 2009;30(14):1771-80.

61 Pérez-Blanco A, Caturla-Such J, Cánovas-Robles J, Sanchez-Payá J. Efficiency of triiodothyronine treatment on organ donor hemodynamic management and adenine nucleotide concentration. Intensive Care Med. 2005;31(7):943-8.

62 Jeevanandam V. Triiodothyronine: spectrum of use in heart transplantation. Thyroid. 1997;7(1):139-45.

63 Goarin JP, Cohen S, Riou B, Jacquens Y, Guesde R, Le Bret F, et al. The effects of triiodothyronine on hemodynamic status and cardiac function in potential heart donors. Anesth Analg. 1996;83(1):41-7.

64 Randell TT, Höckerstedt KA. Triiodothyronine treatment in brain-dead multiorgan donors--a controlled study. Transplantation. 1992;54(4):736-8.ftrdc

65 García-Fages LC, Antolín M, Cabrer C, Talbot R, Alcaraz A, Lozano F, et al. Effects of substitutive triiodothyronine therapy on intracellular nucleotide levels in donor organs. Transplant Proc. 1991;23(5):2495-6.

66 Mariot J, Jacob F, Voltz C, Perrier JF, Strub P. [Value of hormonal treatment with triiodothyronine and cortisone in brain dead patients]. Ann Fr Anesth Reanim. 1991;10(4):321-8. French.

67 Macdonald PS, Aneman A, Bhonagiri D, Jones D, O'Callaghan G, Silvester W, et al. A systematic review and meta-analysis of clinical trials of thyroid hormone administration to brain dead potential organ donors. Crit Care Med. 2012;40(5):1635-44.

68 Rech TH, Moraes RB, Crispim D, Czepielewski MA, Leitão CB. Management of the brain-dead organ donor: a systematic review and meta-analysis. Transplantation. 2013;95(7):966-74.

69 Dhar R, Stahlschmidt E, Marklin G. A randomized trial of intravenous thyroxine for brain-dead organ donors with impaired cardiac function. Prog Transplant. 2020;30(1):48-55.
-7070 Dhar R, Stahlschmidt E, Yan Y, Marklin G. A randomized trial comparing triiodothyronine (T3) with thyroxine (T4) for hemodynamically unstable brain-dead organ donors. Clin Transplant. 2019;33(3):e13486.) Por fim, considerando o potencial benefício do controle glicêmico sobre a função renal, sugere-se manter a glicemia dos potenciais doadores entre 140 a 180mg/dL com administração de insulina subcutânea ou intravenosa.(7171 Hesse UJ, Sutherland DE. Influence of serum amylase and plasma glucose levels in pancreas cadaver donors on graft function in recipients. Diabetes. 1989;38 Suppl 1:1-3.

72 Gores PF, Gillingham KJ, Dunn DL, Moudry-Munns KC, Najarian JS, Sutherland DE. Donor hyperglycemia as a minor risk factor and immunologic variables as major risk factors for pancreas allograft loss in a multivariate analysis of a single institution's experience. Ann Surg. 1992;215(3):217-30.

73 Masson F, Thicoipe M, Gin H, de Mascarel A, Angibeau RM, Favarel-Garrigues JF, et al. The endocrine pancreas in brain-dead donors. A prospective study in 25 patients. Transplantation. 1993;56(2):363-7.

74 Odorico JS, Heisey DM, Voss BJ, Steiner DS, Knechtle SJ, D'Alessandro AM, et al. Donor factors affecting outcome after pancreas transplantation. Transplant Proc. 1998;30(2):276-7.

75 Shaffer D, Madras PN, Sahyoun AI, Simpson MA, Monaco AP. Cadaver donor hyperglycemia does not impair long-term pancreas allograft survival or function. Transplant Proc. 1994;26(2):439-40.

76 Blasi-Ibanez A, Hirose R, Feiner J, Freise C, Stock PG, Roberts JP, et al. Predictors associated with terminal renal function in deceased organ donors in the intensive care unit. Anesthesiology. 2009;110(2):333-41.

77 Perez-Protto SE, Reynolds LF, Dalton JE, Taketomi T, Irefin SA, Parker BM, et al. Deceased donor hyperglycemia and liver graft dysfunction. Prog Transplant. 2014;24(1):106-12.

78 Sally MB, Ewing T, Crutchfield M, Patel MS, Raza S, De La Cruz S, Zatarain J, Malinoski DJ; United Network for Organ Sharing (UNOS) Region 5 Donor Management Goals (DMG) Workgroup. Determining optimal threshold for glucose control in organ donors after neurologic determination of death: a United Network for Organ Sharing Region 5 Donor Management Goals Workgroup prospective analysis. J Trauma Acute Care Surg. 2014;76(1):62-8; discussion 68-9.
-7979 Patel MS, Zatarain J, De La Cruz S, Sally MB, Ewing T, Crutchfield M, et al. The impact of meeting donor management goals on the number of organs transplanted per expanded criteria donor: a prospective study from the UNOS Region 5 Donor Management Goals Workgroup. JAMA Surg. 2014;149(9):969-75.)

Manejo eletrolítico - Foram geradas 3 recomendações referentes ao controle eletrolítico no potencial doador (recomendações 11, 12 e 13 da Tabela 1). A hipernatremia no potencial doador está frequentemente associada à hipovolemia, devendo ser controlada com expansão volêmica, reposição de soluções hipotônicas e controle da poliúria com AVP ou DDAVP, além de monitorizar o sódio sérico objetivando níveis < 155mg/dL.(1111 Kotloff RM, Blosser S, Fulda GJ, Malinoski D, Ahya VN, Angel L, Byrnes MC, DeVita MA, Grissom TE, Halpern SD, Nakagawa TA, Stock PG, Sudan DL, Wood KE, Anillo SJ, Bleck TP, Eidbo EE, Fowler RA, Glazier AK, Gries C, Hasz R, Herr D, Khan A, Landsberg D, Lebovitz DJ, Levine DJ, Mathur M, Naik P, Niemann CU, Nunley DR, O'Connor KJ, Pelletier SJ, Rahman O, Ranjan D, Salim A, Sawyer RG, Shafer T, Sonneti D, Spiro P, Valapour M, Vikraman-Sushama D, Whelan TP; Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Donor Management Task Force. Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med. 2015;43(6):1291-325.,8080 Khosravi MB, Firoozifar M, Ghaffaripour S, Sahmeddini MA, Eghbal MH. Early outcomes of liver transplants in patients receiving organs from hypernatremic donors. Exp Clin Transplant. 2013;11(6):537-40.

81 Kaseje N, McLin V, Toso C, Poncet A, Wildhaber BE. Donor hypernatremia before procurement and early outcomes following pediatric liver transplantation. Liver Transpl. 2015;21(8):1076-81.

82 Mangus RS, Fridell JA, Vianna RM, Milgrom ML, Chestovich P, Vandenboom C, et al. Severe hypernatremia in deceased liver donors does not impact early transplant outcome. Transplantation. 2010;90(4):438-43.

83 Kaczmarek I, Tenderich G, Groetzner J, Deutsch MA, Schulz U, Beiras-Fernandez A, et al. The controversy of donor serum sodium levels in heart transplantation--a multicenter experience. Thorac Cardiovasc Surg. 2006;54(5):313-6.

84 Totsuka E, Dodson F, Urakami A, Moras N, Ishii T, Lee MC, et al. Influence of high donor serum sodium levels on early postoperative graft function in human liver transplantation: effect of correction of donor hypernatremia. Liver Transpl Surg. 1999;5(5):421-8.

85 Dawwas MF, Lewsey JD, Neuberger JM, Gimson AE. The impact of serum sodium concentration on mortality after liver transplantation: a cohort multicenter study. Liver Transpl. 2007;13(8):1115-24.
-8686 Cywinski JB, Mascha E, Miller C, Eghtesad B, Nakagawa S, Vincent JP, et al. Association between donor-recipient serum sodium differences and orthotopic liver transplant graft function. Liver Transpl. 2008;14(1):59-65.) Alterações dos níveis de potássio e de magnésio também são comuns e estão relacionadas a arritmias cardíacas. Sugere-se monitorizar os níveis desses eletrólitos e instituir medidas de correção, visando níveis séricos de potássio entre 3,5 e 5,5mEq/L e de magnésio acima de 1,6mEq/L.(8787 Mousavi SA, Shahabi S, Mostafapour E, Purfakharan M, Fereshtehnejad SM, Amini J, et al. Comparison of the serum electrolyte levels among patients died and survived in the intensive care unit. Tanaffos. 2012;11(4):36-42.

88 Chen M, Sun R, Hu B. [The influence of serum magnesium level on the prognosis of critically ill patients]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2015;27(3):213-7.

89 Kumar S, Honmode A, Jain S, Bhagat V. Does magnesium matter in patients of medical intensive care unit: a study in rural Central India. Indian J Crit Care Med. 2015;19(7):379-83.

90 Velissaris D, Karamouzos V, Pierrakos C, Aretha D, Karanikolas M. Hypomagnesemia in critically ill sepsis patients. J Clin Med Res. 2015;7(12):911-8.

91 Thel MC, Armstrong AL, McNulty SE, Califf RM, O'Connor CM. Randomised trial of magnesium in in-hospital cardiac arrest. Duke Internal Medicine Housestaff. Lancet. 1997;350(9087):1272-6.

92 Smith LF, Heagerty AM, Bing RF, Barnett DB. Intravenous infusion of magnesium sulphate after acute myocardial infarction: effects on arrhythmias and mortality. Int J Cardiol. 1986;12(2):175-83.
-9393 Alves SC, Tomasi CD, Constantino L, Giombelli V, Candal R, Bristot Mde L, et al. Hypomagnesemia as a risk factor for the non-recovery of the renal function in critically ill patients with acute kidney injury. Nephrol Dial Transplant. 2013;28(4):910-6.)

Outros aspectos do manejo do potencial doador

Suporte nutricional - Sugere-se que o aporte nutricional do potencial doador seja continuado caso não haja contraindicações (recomendação 14 da Tabela 1), em razão de potenciais benefícios sobre o trofismo da mucosa intestinal e aumento dos estoques de glicogênio hepático.(77 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult): part II. Mechanical ventilation, endocrine metabolic management, hematological and infectious aspects. Rev Bras Ter Intensiva. 2011;23(3):269-82.,99 Schünemann HJ, Moja L. Reviews: Rapid! Rapid! Rapid! and systematic. Syst Rev. 2015;4(1):4.,5757 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Brand T, Cockfield S, Keshavjee S, Nickerson P, Rao V, Guest C, Young K, Doig C; Pediatric Recommendations Group. Organ donor management in Canada: recommendations of the forum on Medical Management to Optimize Donor Organ Potential. CMAJ. 2006;174(6):S13-32.) É razoável que em indivíduos que já vinham recebendo suporte nutricional pleno, o aporte de calorias seja reduzido em 15% a 30% e que se considere uma oferta calórica mínima (ex.: 500kcal) em potenciais doadores que não vinham recebendo dieta enteral antes do diagnóstico da ME.77 Westphal GA, Caldeira Filho M, Vieira KD, Zaclikevis VR, Bartz MC, Wanzuita R, et al. Guidelines for potential multiple organ donors (adult): part II. Mechanical ventilation, endocrine metabolic management, hematological and infectious aspects. Rev Bras Ter Intensiva. 2011;23(3):269-82.,99 Schünemann HJ, Moja L. Reviews: Rapid! Rapid! Rapid! and systematic. Syst Rev. 2015;4(1):4.,5757 Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Brand T, Cockfield S, Keshavjee S, Nickerson P, Rao V, Guest C, Young K, Doig C; Pediatric Recommendations Group. Organ donor management in Canada: recommendations of the forum on Medical Management to Optimize Donor Organ Potential. CMAJ. 2006;174(6):S13-32.,9494 Powner DJ. Factors during donor care that may affect liver transplantation outcome. Prog Transplant. 2004;14(3):241-7; quiz 248-9.

95 Adam R, Reynes M, Bao YM, Astarcioglu I, Azoulay D, Chiche L, et al. Impact of glycogen content of the donor liver in clinical liver transplantation. Transplant Proc. 1993;25(1 Pt 2):1536-7.

96 Powner DJ, Bernstein IM. Extended somatic support for pregnant women after brain death. Crit Care Med. 2003;31(4):1241-9.
-9797 Dominguez-Roldan JM, Murillo-Cabezas F, Santamaria-Mifsut JL, Muñoz-Sanchez A, Villen-Nieto J, Barrera-Chacon JM. Changes in resting energy expenditure after development of brain death. Transplant Proc. 1995;27(4):2397-8.)

Infecção e sepse - O risco de transmissão de infecção bacteriana entre doadores e receptores de órgãos é baixo e a infecção no doador não parece comprometer os desfechos. Recomenda-se utilizar antibióticos no potencial doador que apresente infecção ou sepse (recomendação 15 da Tabela 1). Os riscos de transmissão de infecção são menores com antibioticoterapia apropriada no potencial doador por no mínimo 24 horas, seguida de manutenção do antibiótico no receptor por 7 a 14 dias.(9898 Little DM, Farrell JG, Cunningham PM, Hickey DP. Donor sepsis is not a contraindication to cadaveric organ donation. QJM. 1997;90(10):641-2.

99 Zibari GB, Lipka J, Zizzi H, Abreo KD, Jacobbi L, McDonald JC. The use of contaminated donor organs in transplantation. Clin Transplant. 2000;14(4 Pt 2):397-400.

100 Lumbreras C, Sanz F, González A, Pérez G, Ramos MJ, Aguado JM, et al. Clinical significance of donor-unrecognized bacteremia in the outcome of solid-organ transplant recipients. Clin Infect Dis. 2001;33(5):722-6.

101 Caballero F, Lopez-Navidad A, Perea M, Cabrer C, Guirado L, Solà R. Successful liver and kidney transplantation from cadaveric donors with left-sided bacterial endocarditis. Am J Transplant. 2005;5(4 Pt 1):781-7.

102 Len O, Gavaldà J, Blanes M, Montejo M, San Juan R, Moreno A, Carratalà J, de la Torre-Cisneros J, Bou G, Cordero E, Muñoz P, Cuervas-Mons V, Alvarez MT, Borrell N, Fortun J, Pahissa A; Spanish Research Network for the Study of Infection in Transplantation. Donor infection and transmission to the recipient of a solid allograft. Am J Transplant. 2008;8(11):2420-5.

103 Sözen H, Fidan K, Mahli A, Singin E, Buyan N, Sindel S, et al. Successful solid organ transplantation from septicemic cadaveric donors: case report. Transplant Proc. 2008;40(1):299-301.

104 Lin TL, Kuo SC, Yeh CH, Chan YC, Lin YH, Li WF, et al. Donor-transmitted bacterial infection in deceased donor liver transplantation: experience of Southern Taiwan Medical Center. Transplant Proc. 2018;50(9):2711-4.

105 Corman Dincer P, Tore Altun G, Birtan D, Arslantas R, Sarici Mert N, Özdemir I, et al. Incidence and risk factors for systemic infection in deceased donors. Transplant Proc. 2019;51(7):2195-7.

106 Kubak BM, Gregson AL, Pegues DA, Leibowitz MR, Carlson M, Marelli D, et al. Use of hearts transplanted from donors with severe sepsis and infectious deaths. J Heart Lung Transplant. 2009;28(3):260-5.
-107107 Outerelo C, Gouveia R, Mateus A, Cruz P, Oliveira C, Ramos A. Infected donors in renal transplantation: expanding the donor pool. Transplant Proc. 2013;45(3):1054-6.) Além disso, deve-se coletar culturas de todos os potenciais doadores em diferentes sítios, bem como a administrar antibióticos, preferencialmente guiados por culturas, aos receptores.(100100 Lumbreras C, Sanz F, González A, Pérez G, Ramos MJ, Aguado JM, et al. Clinical significance of donor-unrecognized bacteremia in the outcome of solid-organ transplant recipients. Clin Infect Dis. 2001;33(5):722-6.,108108 Freeman RB, Giatras I, Falagas ME, Supran S, O'Connor K, Bradley J, et al. Outcome of transplantation of organs procured from bacteremic donors. Transplantation. 1999;68(8):1107-11.

109 Cerutti E, Stratta C, Romagnoli R, Serra R, Lepore M, Fop F, et al. Bacterial- and fungal-positive cultures in organ donors: clinical impact in liver transplantation. Liver Transpl. 2006;12(8):1253-9.

110 Angelis M, Cooper JT, Freeman RB. Impact of donor infections on outcome of orthotopic liver transplantation. Liver Transpl. 2003;9(5):451-62.
-111111 Ruiz I, Gavaldà J, Monforte V, Len O, Román A, Bravo C, et al. Donor-to-host transmission of bacterial and fungal infections in lung transplantation. Am J Transplant. 2006;6(1):178-82.)

Controle da temperatura corporal - Foram geradas duas recomendações referentes ao controle da temperatura corporal (recomendações 16 e 17 da Tabela 1). Na presença de instabilidade hemodinâmica, sugere-se manter o potencial doador em normotermia (> 35oC) para reduzir o risco de arritmias, disfunção cardiovascular e parada cardíaca. Por outro lado, entre potenciais doadores estáveis do ponto de vista hemodinâmico, a indução de hipotermia moderada (34 - 35oC) está associada com melhor função do enxerto renal, contudo esse procedimento requer a monitorização da temperatura central, não disponível em todas as UTIs.(112112 Niemann CU, Feiner J, Swain S, Bunting S, Friedman M, Crutchfield M, et al. Therapeutic hypothermia in deceased organ donors and kidney-graft function. N Engl J Med. 2015;373(5):405-14.

113 Schnuelle P, Mundt HM, Drüschler F, Schmitt WH, Yard BA, Krämer BK, et al. Impact of spontaneous donor hypothermia on graft outcomes after kidney transplantation. Am J Transplant. 2018;18(3):704-14.

114 Schnuelle P, Benck U, Krämer BK, Yard BA, Zuckermann A, Wagner F, et al. Impact of donor core body temperature on graft survival after heart transplantation. Transplantation. 2018;102(11):1891-900.

115 Huang FY, Huang BT, Wang PJ, Zuo ZL, Heng Y, Xia TL, et al. The efficacy and safety of prehospital therapeutic hypothermia in patients with out-of-hospital cardiac arrest: a systematic review and meta-analysis. Resuscitation. 2015;96:170-9.
-116116 Axelrod DA, Malinoski D, Patel MS, Broglio K, Lewis R, Groat T, et al. Modeling the economic benefit of targeted mild hypothermia in deceased donor kidney transplantation. Clin Transplant. 2019;33(7):e13626.)

Transfusão de hemácias - A anemia pode comprometer a entrega de oxigênio aos órgãos que se pretende preservar para transplante. Por não conhecermos os níveis de hemoglobina necessários para contribuir com o transporte adequado de oxigênio em potenciais doadores, sugere-se transfundir hemácias quando a hemoglobina for menor que 7g/dL, de acordo com a prática habitual em outros pacientes críticos (recomendação 18 da Tabela 1).(117117 de la Cruz JS, Sally MB, Zatarain JR, Crutchfield M, Ramsey K, Nielsen J, et al. The impact of blood transfusions in deceased organ donors on the outcomes of 1,884 renal grafts from United Network for Organ Sharing Region 5. J Trauma Acute Care Surg. 2015;79(4 Suppl 2):S164-70.)

Protocolos guiados por metas - A adoção de protocolos de manutenção do potencial doador guiados por checklists de metas clínicas pode contribuir para o aumento do número de órgãos doados, influenciar a função do enxerto e diminuir perdas de potenciais doadores por parada cardíaca. De uma forma geral os desfechos estão associados ao número de metas alcançadas durante a manutenção do potencial doador, o que inclui metas ventilatórias, hemodinâmicas e de manejo endócrino-metabólico.(2424 Westphal GA, Coll E, de Souza RL, Wagner S, Montemezzo A, Cani de Souza FC, et al. Positive impact of a clinical goal-directed protocol on reducing cardiac arrests during potential brain-dead donor maintenance. Crit Care. 2016;20(1):323.,2828 Minambres E, Coll E, Duerto J, Suberviola B, Mons R, Cifrian JM, et al. Effect of an intensive lung donor-management protocol on lung transplantation outcomes. J Heart Lung Transplant. 2014;33:178-84.,2929 Miñambres E, Pérez-Villares JM, Chico-Fernández M, Zabalegui A, Dueñas-Jurado JM, Misis M, et al. Lung donor treatment protocol in brain dead-donors: a multicenter study. J Heart Lung Transplant. 2015;34(6):773-80.,7979 Patel MS, Zatarain J, De La Cruz S, Sally MB, Ewing T, Crutchfield M, et al. The impact of meeting donor management goals on the number of organs transplanted per expanded criteria donor: a prospective study from the UNOS Region 5 Donor Management Goals Workgroup. JAMA Surg. 2014;149(9):969-75.,118118 van Erp AC, van Dullemen LF, Ploeg RJ, Leuvenink HG. Systematic review on the treatment of deceased organ donors. Transplant Rev (Orlando). 2018;32(4):194-206.

119 Rosendale JD, Chabalewski FL, McBride MA, Garrity ER, Rosengard BR, Delmonico FL, et al. Increased transplanted organs from the use of a standardized donor management protocol. Am J Transplant. 2002;2(8):761-8.

120 Salim A, Velmahos GC, Brown C, Belzberg H, Demetriades D. Aggressive organ donor management significantly increases the number of organs available for transplantation. J Trauma. 2005;58(5):991-4.

121 Salim A, Martin M, Brown C, Rhee P, Demetriades D, Belzberg H. The effect of a protocol of aggressive donor management: implications for the national organ donor shortage. J Trauma. 2006;61(2):429-33; discussion 433-5.

122 Malinoski DJ, Daly MC, Patel MS, Oley-Graybill C, Foster CE 3rd, Salim A. Achieving donor management goals before deceased donor procurement is associated with more organs transplanted per donor. J Trauma. 2011;71(4):990-5; discussion 996.

123 Malinoski DJ, Patel MS, Daly MC, Oley-Graybill C, Salim A; UNOS Region 5 DMG workgroup. The impact of meeting donor management goals on the number of organs transplanted per donor: results from the United Network for Organ Sharing Region 5 prospective donor management goals study. Crit Care Med. 2012;40(10):2773-80.

124 Marshall GR, Mangus RS, Powelson JA, Fridell JA, Kubal CA, Tector AJ. Donor management parameters and organ yield: single center results. J Surg Res. 2014;191(1):208-13.

125 Patel MS, De La Cruz S, Sally MB, Groat T, Malinoski DJ. Active donor management during the hospital phase of care is associated with more organs transplanted per donor. J Am Coll Surg. 2017;225(4):525-31.

126 Malinoski DJ, Patel MS, Ahmed O, Daly MC, Mooney S, Graybill CO, Foster CE, Salim A; United Network for Organ Sharing (UNOS) Region 5 Donor Management Goals (DMG) Workgroup. The impact of meeting donor management goals on the development of delayed graft function in kidney transplant recipients. Am J Transplant. 2013;13(4):993-1000.
-127127 Westphal GA, Zaclikevis VR, Vieira KD, Cordeiro RB, Horner MB, Oliveira TP, et al. A managed protocol for treatment of deceased potential donors reduces the incidence of cardiac arrest before organ explant. Rev Bras Ter Intensiva. 2012;24(4):334-40.) Sugere-se, portanto, utilizar protocolos guiados por metas durante o manejo de potenciais doadores.

DISCUSSÃO

A presente diretriz pretende fornecer recomendações para otimização do manejo clínico do potencial doador baseado nas evidências disponíveis, visando incrementar a qualidade dos órgãos ofertados e reduzir perdas de doadores.

Esta diretriz avaliou um grande volume de intervenções e conduzimos uma rigorosa busca norteada pela metodologia PICO para prover recomendações baseadas em métodos padronizados de revisão rápida da literatura.(99 Schünemann HJ, Moja L. Reviews: Rapid! Rapid! Rapid! and systematic. Syst Rev. 2015;4(1):4.,1010 Haby MM, Chapman E, Clark R, Barreto J, Reveiz L, Lavis JN. Designing a rapid response program to support evidence-informed decision-making in the Americas region: using the best available evidence and case studies. Implement Sci. 2016;11(1):117.) Limitações em potencial estão relacionadas à baixa ou muito baixa confiança na evidência identificada para muitas das questões e o uso de evidências indiretas, que não modificaram após a atualização da revisão da literatura. Entretanto, as recomendações para manejo do potencial doador são consistentes com documentos similares recentemente publicados.(1111 Kotloff RM, Blosser S, Fulda GJ, Malinoski D, Ahya VN, Angel L, Byrnes MC, DeVita MA, Grissom TE, Halpern SD, Nakagawa TA, Stock PG, Sudan DL, Wood KE, Anillo SJ, Bleck TP, Eidbo EE, Fowler RA, Glazier AK, Gries C, Hasz R, Herr D, Khan A, Landsberg D, Lebovitz DJ, Levine DJ, Mathur M, Naik P, Niemann CU, Nunley DR, O'Connor KJ, Pelletier SJ, Rahman O, Ranjan D, Salim A, Sawyer RG, Shafer T, Sonneti D, Spiro P, Valapour M, Vikraman-Sushama D, Whelan TP; Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Donor Management Task Force. Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med. 2015;43(6):1291-325.,128128 Ball IM, Hornby L, Rochwerg B, Weiss MJ, Gillrie C, Chassé M, et al. Management of the neurologically deceased organ donor: a Canadian clinical practice guideline. CMAJ. 2020;192(14):E361-E369.,129129 Meyfroidt G, Gunst J, Martin-Loeches I, Smith M, Robba C, Taccone FS, et al. Management of the brain-dead donor in the ICU: general and specific therapy to improve transplantable organ quality. Intensive Care Med. 2019;45(3):343-53.)

Alguns estudos observacionais têm demonstrado que a adoção de checklists para guiar o manejo do potencial doador pode auxiliar na redução de paradas cardíacas em potenciais doadores e aumentar o número de órgãos doados por doador.(2424 Westphal GA, Coll E, de Souza RL, Wagner S, Montemezzo A, Cani de Souza FC, et al. Positive impact of a clinical goal-directed protocol on reducing cardiac arrests during potential brain-dead donor maintenance. Crit Care. 2016;20(1):323.,7979 Patel MS, Zatarain J, De La Cruz S, Sally MB, Ewing T, Crutchfield M, et al. The impact of meeting donor management goals on the number of organs transplanted per expanded criteria donor: a prospective study from the UNOS Region 5 Donor Management Goals Workgroup. JAMA Surg. 2014;149(9):969-75.,120120 Salim A, Velmahos GC, Brown C, Belzberg H, Demetriades D. Aggressive organ donor management significantly increases the number of organs available for transplantation. J Trauma. 2005;58(5):991-4.,122122 Malinoski DJ, Daly MC, Patel MS, Oley-Graybill C, Foster CE 3rd, Salim A. Achieving donor management goals before deceased donor procurement is associated with more organs transplanted per donor. J Trauma. 2011;71(4):990-5; discussion 996.,123123 Malinoski DJ, Patel MS, Daly MC, Oley-Graybill C, Salim A; UNOS Region 5 DMG workgroup. The impact of meeting donor management goals on the number of organs transplanted per donor: results from the United Network for Organ Sharing Region 5 prospective donor management goals study. Crit Care Med. 2012;40(10):2773-80.,125125 Patel MS, De La Cruz S, Sally MB, Groat T, Malinoski DJ. Active donor management during the hospital phase of care is associated with more organs transplanted per donor. J Am Coll Surg. 2017;225(4):525-31.,127127 Westphal GA, Zaclikevis VR, Vieira KD, Cordeiro RB, Horner MB, Oliveira TP, et al. A managed protocol for treatment of deceased potential donors reduces the incidence of cardiac arrest before organ explant. Rev Bras Ter Intensiva. 2012;24(4):334-40.,130130 Helms AK, Torbey MT, Hacein-Bey L, Chyba C, Varelas PN. Standardized protocols increase organ and tissue donation rates in the neurocritical care unit. Neurology. 2004;63(10):1955-7.,131131 Franklin GA, Santos AP, Smith JW, Galbraith S, Harbrecht BG, Garrison RN. Optimization of donor management goals yields increased organ use. Am Surg. 2010;76(6):587-94.) Nesse contexto, utilizamos as principais recomendações da presente diretriz para elaborarmos um checklist (Figura 1) de metas clínicas baseado em evidências, com o propósito de fornecer subsídios aos coordenadores de transplantes e profissionais de UTI para otimização do cuidado ao potencial doador.

Por outro lado, considerando que os estudos que ressaltam o papel do checklist de manejo do potencial doador são de caráter observacional, não há evidências suficientemente consistentes para apoiar o uso sistemático de checklists no cuidado do potencial doador. Assim, propusemos o Donation Network to Optimise Organ Recovery Study (DONORS; NCT03179020) um ensaio clínico multicêntrico randomizado por clusters que pretende testar a efetividade da implementação de um checklist contendo metas e recomendações de cuidados, na redução de perdas de doadores de órgãos por parada cardíaca e aumentar o número de órgãos doados por doador.(132132 Westphal GA, Robinson CC, Biasi A, Machado FR, Rosa RG, Teixeira C, de Andrade J, Franke CA, Azevedo LCP, Bozza F, Guterres CM, da Silva DB, Sganzerla D, do Prado DZ, Madalena IC, Rohden AI, da Silva SS, Giordani NE, Andrighetto LV, Benck PS, Roman FR, de Melo MFRB, Pereira TB, Grion CMC, Diniz PC, Oliveira JFP, Mecatti GC, Alves FAC, Moraes RB, Nobre V, Hammes LS, Meade MO, Nothen RR, Falavigna M; DONORS (Donation Network to Optimise Organ Recovery Study) Investigators and the BRICNet. DONORS (Donation Network to Optimise Organ Recovery Study): Study protocol to evaluate the implementation of an evidence-based checklist for brain-dead potential organ donor management in intensive care units, a cluster randomised trial. BMJ Open. 2019;9(6):e028570.) A implementação do checklist deve ser precedida de treinamento adequado das equipes de terapia intensiva e de coordenadores de transplantes. Sugere-se que o checklist seja aplicado à beira do leito imediatamente após o primeiro exame clínico para determinação da ME, e sua aplicação repetida, idealmente, a cada 6 horas até a retirada dos órgãos para transplantes. Sugere-se também que um membro da coordenação de transplante ou um profissional designado da UTI ou emergência aplique o checklist à beira do leito. O mesmo profissional também será responsável por solicitar pessoalmente ao médico que modifique a conduta clínica se for observado algum aspecto inadequado do tratamento de acordo com o checklist.

DECLARAÇÕES

Disponibilidade de dados e matérias: todo o material relevante está contido no artigo e nos materiais complementares.

Financiamento: Esta diretriz foi financiada pelo Ministério da Saúde com recursos do Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS). Os patrocinadores não tiveram papel na coordenação desta diretriz.

Contribuição dos autores: Todos os autores, exceto AR, DFSP, FDP, RCM, e RRN, participaram de pelo menos um dos painéis de especialistas. Todos os autores revisaram e aprovaram a versão final do manuscrito. A contribuição detalhada de cada autor está disponível no material suplementar.

Agradecimentos: Os autores agradecem às seguintes instituições pelo seu suporte: Ministério da Saúde a Coordenação Geral do Sistema Nacional de Transplantes (CGSNT), Hospital Moinhos de Vento, Associação Brasileira de Transplantes de Órgãos (ABTO), Associação de Medicina Intensiva Brasileira (AMIB) e seu Comitê de Doação e Transplante, e a Brazilian Research in Intensive Care Network (BRICNet).

Permissão: A publicação deste documento na RBTI foi previamente autorizada pela Departamento de permissões do periódico Annals of Intensive Care, nos seguintes termos:

Por ser o Annals of Intensive Care um periódico totalmente em acesso aberto usando uma licença CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/), você pode publicar e traduzir em português as diretrizes. O único requisito é que a RBTI dê crédito ao artigo original e indique quais alterações foram feitas, se houver.

Assim, declaramos que as alterações realizadas no presente documento resumem-se à condensação da sustentação teórica das recomendações e da sessão de discussão, mantendo-se integralmente o conteúdo das recomendações.

  • Este artigo é uma compilação das Diretrizes brasileiras para o manejo de potenciais doadores de órgãos em morte encefálica. Uma forçatarefa da AMIB, ABTO, BRICNet e Coordenação Geral do Sistema Nacional de Transplantes; publicado originalmente no Westphal GA, Robinson CC, Cavalcanti AB, Gonçalves ARR, Guterres CM, Teixeira C, Stein C, Franke CA, da Silva DB, Pontes DFS, Nunes DSL, Abdala E, Dal-Pizzol F, Bozza FA, Machado FR, de Andrade J, Cruz LN, de Azevedo LCP, Machado MCV, Rosa RG, Manfro RC, Nothen RR, Lobo SM, Rech TH, Lisboa T, Colpani V, Falavigna M. Brazilian guidelines for the management of brain-dead potential organ donors. The task force of the AMIB, ABTO, BRICNet, and the General Coordination of the National Transplant System. Ann Intensive Care. 2020;10(1):169. doi: 10.1186/s13613-020-00787-0. PMID: 33315161; PMCID: PMC7736434.

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Datas de Publicação

  • Publicação nesta coleção
    19 Abr 2021
  • Data do Fascículo
    Jan-Mar 2021

Histórico

  • Recebido
    08 Dez 2020
  • Aceito
    15 Dez 2020
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