Brazilian guidelines for the management of brain-dead potential organ donors. The task force of the Associação de Medicina Intensiva Brasileira, Associação Brasileira de Transplantes de Órgãos, Brazilian Research in Critical Care Network, and the General Coordination of the National Transplant System

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 About the authors

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

INTRODUCTION

The progress of the process of organ donation for transplantation is essential to increase the deceased-donor pool and to decrease the growing disparity between the number of patients on transplant waiting lists and the availability of organs.(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.) This process includes the identification of the potential donor, diagnosis of brain death, family support and interview, evaluation of donor eligibility criteria, clinical management of the potential organ donor, and organ procurement and distribution.(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.) Given the marked clinical instability that occurs in patients who progress to brain death, the application of potential-donor management strategies is crucial to avoid loss of organs due to hypoperfusion or loss of donors due to cardiac arrest.(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.

The recommendations presented in this guideline intend to promote a general approach to mitigate the disparity between supply and demand of organs for transplantation.

OBJECTIVE

To provide recommendations to guide the clinical management of brain-dead potential organ donors aiming to reduce the rate of cardiac arrest of the potential donor and to improve organ viability for transplantation.

METHODS

The present document provides a partial update on the 2011 Brazilian Guidelines for Management of Adult Potential Multiple-Organ Deceased Donors.(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.) The target audience of this guideline is health care professionals, especially physicians and nursing staff working in adult intensive care units (ICUs) and emergency departments, who are involved in the care of adult individuals with known or suspected brain death.

The clinical issues addressed by the guideline were divided into the following major topics: (1) ventilatory support; (2) hemodynamic support; (3) endocrine, metabolic and nutritional management; (4) specific aspects that include infection and sepsis, red blood cell transfusion, and body temperature control; and (5) goal-directed therapy. For each clinical issue, operational questions were developed and framed using the population-intervention-comparison-outcome (PICO) format. The population of interest consists of potential organ donors with known or suspected brain death,(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.) hereafter referred to as potential donors. The outcomes considered for decision-making were cardiac arrest, the number of organs recovered or transplanted per donor, and graft function or graft survival.

For each clinical issue, rapid systematic reviews(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.) were conducted using the following search strategy: (1) Review of the reference lists of Brazilian guidelines(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.) and the 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.) statement on the management of the potential organ donor; (2) Review of related topics in the DynaMed and UpToDate databases; and (3) PubMed search focusing on systematic reviews and clinical trials published until October 2016 and until January 2017. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.(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.

The recommendations were prepared and submitted to 2 face-to-face expert panels held in November 2016, and February 2017. For each recommendation, the direction of the course of action was discussed (whether to perform or not to perform the proposed action), and the strength of the recommendation was classified as strong or weak according to the GRADE system.(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.) After the last panel meeting, a new systematic search covering the period from October 2016 to May 2020 was carried out to identify new evidence that could potentially modify the recommendations. From June to July 2020, a Delphi process was performed with the panelists to present the results of the literature update and review the direction and strength of 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 as good clinical practice. Table 1 shows a summary of the recommendations and figure 1 presents the checklist based on the main recommendations to assist in bedside monitoring of clinical goals related to the recommendations and in the application of the management strategies. Figure 2 depicts graphically the flow of the recommendations along the clinical management.

Table 1
Summary of recommendations
Figure 1
Evidence-based bed-side checklist for clinical management of brain-dead potential organ donors.

SaO2 - arterial oxygen saturation; FiO2 - fraction of inspired oxygen; PEEP - positive end-expiratory pressure; Vt - tidal volume; MAP - mean arterial pressure; ΔPp - pulse pressure respiratory variation; ΔMAP - mean arterial pressure variation; ΔSV - stroke volume respiratory variation; CVP - central venous pressure; Na+ - sodium; K+ - potassium; Mg++ -magnesium; Hb - hemoglobin; NA - not available/not applicable.


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.


Ventilatory support recommendations

Two recommendations directed to ventilatory care (recommendations 1 and 2 in Table 1) were generated, with emphasis on the use of the protective ventilation strategy, which consists of the association of tidal volume of 6 to 8mL/kg and positive end-expiratory pressure (PEEP) of 8 to 10cmH2O in potential donors with normal lungs, in addition to the suggestion not using alveolar recruitment maneuvers routinely. As practical considerations, we added the possibility of associating the continuous positive pressure apnea test (CPAP) to the protective strategy, to avoid hypoxemia during the test, as well as the fractional inspired oxygen (FiO2) and PEEP titration aiming at an arterial oxygen saturation (SaO2) > 90% to favor the oxygenation of tissues.(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.

Hemodynamic support recommendations

Three recommendations were generated about hemodynamic care (recommendations 3 to 5 in Table 1). It is suggested the use of 30mL/kg crystalloid aliquots in potential donors who are hypotensive (mean arterial pressure - MAP < 65mmHg) and with signs of fluid-responsiveness (preferably measured with dynamic parameters), in order to mitigate the occurrence of volume overload.(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.

If the pressure goal of MAP ≥ 65mmHg is not achieved with the initial volume expansion, immediate norepinephrine infusion should be started to achieve this target.(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.) The use of dopamine can be considered in cases of bradycardia with signs of low cardiac output,(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.) but its potential of dopamine should be considered.(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.) The administration of low doses of dopamine is not recommended, as the survival benefits of renal and cardiac grafts are not clear and as its potential arrhythmogenic effect increases the risks of cardiac arrest.(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.

Endocrine and electrolyte management recommendations

Endocrine management - In table 1 there are five recommendations regarding endocrine management, referring to the use of arginine-vasopressin (AVP), hydrocortisone, desmopressin (DDAVP), thyroid hormones and insulin (recommendations 6, 7, 8, 9 and 10 in Table 1, respectively). The administration of AVP (initial bolus of 1 IU followed by the infusion of 0.5 IU/hour to 2.4 IU/hour) and hydrocortisone (100mg intravenous every 8 hours) in potential donors using norepinephrine or dopamine decreases the requirement for adrenergic vasopressors, is associated with a lower incidence of cardiovascular deterioration and contributes to the control of polyuria when diabetes insipidus is present.(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.) Arginine-vasopressin and hydrocortisone should be started at the same time as the adrenergic vasopressor infusion begins. Desmopressin is indicated to control polyuria (diuresis > 4mL/kg/hour) in potential donors with diabetes insipidus who maintain adequate blood pressure without adrenergic vasopressors. Arginine-vasopressin and DDAVP can be associated in refractory cases.(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.) Although the intranasal route is possible, the preferred route is intravenous, in doses of 1 - 2µg every 2 to 4 hours,(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.) until a diuresis < 4mL/kg/hour is obtained.(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.) Although brain death is associated with a drop in thyroid hormone levels, there is no evidence to justify its use in the potential donor, even in potential donors with hemodynamic instability or impaired cardiac function.(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.) Finally, considering the potential benefit of glycemic control over renal function, it is suggested to keep the blood glucose of potential donors between 140 to 180mg/dL with administration of subcutaneous or intravenous insulin.(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.

Electrolytic management - Three recommendations were generated regarding electrolytic control in the potential donor (recommendations 11, 12 and 13 in Table 1). Hypernatremia in the potential donor is often associated with hypovolemia, and should be controlled with volume expansion, replacement of hypotonic solutions and polyuria control with AVP or DDAVP, in addition to monitoring serum sodium for levels < 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.) Changes in potassium and magnesium levels are also common and are related to cardiac arrhythmias. It is suggested to monitor the levels of these electrolytes and institute corrective measures, aiming at serum levels of potassium between 3.5 and 5.5mEq/L and of magnesium above 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.

Other aspects of potential donor management

Nutritional support - It is suggested that the nutritional supply of the potential donor be continued if there are no contraindications (recommendation 14 in Table 1), due to the potential benefits on intestinal mucosal trophism and increased hepatic glycogen stores.(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.) In individuals who have already been receiving full nutritional support, the calorie intake should be reduced by 15% to 30%, in addition to considering a minimum caloric supply (eg 500kcal) in potential donors who have not been receiving enteral diet before diagnosis of brain death.(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.

Infection and sepsis - The risk of transmission of bacterial infection between organ donors and recipients is low and the infection in the donor does not appear to compromise the outcomes. It is recommended to use antibiotics in the potential donors who present infection or sepsis (recommendation 15 in Table 1). The risks of infection transmission are lower with appropriate antibiotic therapy in the potential donor for at least 24 hours, followed by maintenance of the antibiotic in the recipient for 7 to 14 days.(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.) In addition, cultures of all potential donors should be collected from different sites, as well as antibiotics administered to recipients, preferably guided by cultures.(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.

Control of body temperature - Two recommendations were generated regarding the control of body temperature (recommendations 16 and 17 in Table 1). In the presence of hemodynamic instability, it is suggested to keep the potential donor in normothermia (> 35oC) to reduce the risk of arrhythmias, cardiovascular dysfunction and cardiac arrest. On the other hand, among potential donors who are hemodynamically stable, the induction of moderate hypothermia (34 - 35oC) has been associated with better renal graft function, however this procedure requires monitoring of central temperature, which is not always available in all ICUs.(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.

Red blood cell transfusion- Anemia can compromise the delivery of oxygen to the organs that are intended to be preserved for transplantation. As we do not know the hemoglobin levels necessary to contribute to the adequate transport of oxygen in potential donors, it is suggested to transfuse red blood cells when the hemoglobin is less than 7g/dL, according to the usual practice in other critical patients (recommendation 18 of the Table 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.

Goal-guided protocols - The adoption of goal-directed checklists to guide the maintenance of potential donor can contribute to the increase in the number of donated organs, influence the function of the graft and decrease losses of potential donors due to cardiac arrest. In general, the outcomes are associated with the number of goals achieved during the maintenance of the potential donor, which includes ventilatory, hemodynamic and endocrine-metabolic management goals.(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.) Therefore, it is suggested to use goal-guided protocols during the management of potential donors.

DISCUSSION

The present guideline aimed to provide parameters to optimize the clinical management of potential donors based on the available evidence, aiming to improve the quality of organs for transplantation and to reduce donor losses.

This guideline evaluated a broad volume of treatments and we performed rigorous PICO-driven research to provide the recommendations based on standardized rapid review methods.(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.) Potential limitations are the low or very low certainty in the evidence identified for many of the questions, and indirect evidence that did not change after the systematic review update. However, management recommendations are consistent with similar documents recently published.(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.

Some observational studies have reported that the application of a checklist to guide the management of brain-dead potential donors may help reduce the rate of cardiac arrest in potential donors and increase the number of organs recovered per donor.(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.) In this context, we used the main recommendations of the present guideline to develop an evidence-based clinical goal-directed checklist (Figure 1) with the purpose of providing transplant coordinators and ICU professionals with essential information to optimize the care of potential donors.

However, because the available studies highlighting the role of potential donor management checklists are observational, there is insufficient evidence to support the systematic use of checklists in the management of potential donors. Therefore, we proposed the Donation Network to Optimize Organ Recovery Study (DONORS; NCT03179020), which is a parallel cluster randomized controlled multicenter trial that aims to test the effectiveness of the implementation of a checklist containing goals and recommendations of care in reducing organ donor losses due to cardiac arrest and increasing the number of organs recovered per donor.(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.) The implementation of the checklist should be preceded by the appropriate training of intensive care teams and transplant coordinators. We suggest applying the checklist at the bedside immediately after the first clinical examination for the diagnosis of brain death, repeating the application, ideally, every 6 hours until organ procurement for transplantation. We also suggest that a member of the transplant coordination office or a designated professional of the ICU or emergency department apply the checklist at the bedside. The same individual will also be responsible for personally prompting the physician in charge to modify the clinical management if any inappropriate aspect of care, according to the checklist, is noted.

DECLARATIONS

Availability of data and material: All relevant data are within the paper and its Supporting Information files.

Funding: This guideline was funded by the Brazilian Ministry of Health through the Programa de Apoio ao Desenvolvimento Institucional do Sistema Único de Saúde (PROADI-SUS). The funding body has no role in the coordination of the guideline.

Authors’ contributions: All authors, except for AR, DFSP, FDP, RCM, and RRN, participated in at least one of the expert panels. All authors read and approved the final manuscript. The detailed contribution of each author is presented in supplementary material.

Acknowledgments: The authors thank the Brazilian Ministry of Health and the General Coordenação Geral do Sistema Nacional de Transplantes (CGSNT), as well as Hospital Moinhos de Vento, the Associação Brasileira de Transplantes de Órgãos (ABTO), the Associação de Medicina Intensiva Brasileira (AMIB) Committee for Organ Donation for Transplant, and the Brazilian Research in Intensive Care Network (BRICNet) for their support.

Permission: The publication of this document in RBTI was previously authorized by Permission dept of the Annals of Intensive Care Journal, according to the following terms:

Being Annals of Intensive Care a fully Open Access journal using a CC-BY 4.0 license (https://creativecommons.org/licenses/by/4.0/), you can publish and translate in Portuguese the guidelines. The only requirement is that RBTI provides credit to the original article and indicate what changes are made, if any.

Therefore, we declare that the changes made in this document are limited to the condensation of the theoretical support of the recommendations and the discussion session, maintaining the content of the recommendations in full.

  • This article is a compilation of the 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; originally published in the 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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Publication Dates

  • Publication in this collection
    19 Apr 2021
  • Date of issue
    Jan-Mar 2021

History

  • Received
    08 Dec 2020
  • Accepted
    15 Dec 2020
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