J Korean Soc Transplant.  2015 Sep;29(3):89-100. 10.4285/jkstn.2015.29.3.89.

Optimal Management of Brain Death Donor

• Gil E
• Park JB

• KMID: 2202581
• DOI: http://doi.org/10.4285/jkstn.2015.29.3.89

Abstract

Since the Harvard criteria for brain death was proposed in 1968, deceased donor, mainly brain death donor (BD), organ transplantation has been performed worldwide and given the chance for a new life to patients suffering from end-stage organ disease. In Korea by the eager efforts promoting brain-dead organ donation, fortunately, the number of organ donations from the brain-dead has increased successfully in the last decade. However, the disparity between the number of patients awaiting organ transplantation on the list and the number of actual organ donations has become wider and the organ shortage remains a limitation for new lives by transplantation. Because of donor organ restriction, optimal management of brain-dead donors is increasingly important. In addition, the favorable clinical outcomes of recipients is directly associated with the well-preserved organ function of brain-dead donors, which can be accomplished by the maintenance of optimal perfusion. However the brain-dead condition leads to various and profound pathophysiological changes in the neuroendocrine and cardiovascular systems, and management of brain-dead organ donors usually includes active intensive care for maintaining organ function. Therefore, to enhance the potential organ graft function and increase the organ supply, physicians must have knowledge of the pathophysiology of brain death and must deal with rapid hemodynamic changes, endocrine and metabolic abnormalities, and respiratory complications. This article reviews the pathophysiologic changes resulting from brain death and the adequate management for maximizing use of organs recovered from brain death donors.

Keyword

Brain death; Organ donor; Hemodynamics; Hormone replacement therapy

MeSH Terms

Brain Death*
Brain*
Cardiovascular System
Critical Care
Hemodynamics
Hormone Replacement Therapy
Humans
Korea
Organ Transplantation
Perfusion
Tissue and Organ Procurement
Tissue Donors*
Transplants

Figure

• 

  Fig. 1. Factors causing hemodynamic instability in the potential organ donor.

Reference

References

1). Singbartl K, Murugan R, Kaynar AM, Crippen DW, Tisherman SA, Shutterly K, et al. Intensivist-led management of brain-dead donors is associated with an increase in organ recovery for transplantation. Am J Transplant. 2011; 11:1517–21.

2). Shemie SD, Ross H, Pagliarello J, Baker AJ, Greig PD, Brand T, et al. Organ donor management in Canada: recommendations of the forum on Medical Management to Optimize Donor Organ Potential. CMAJ. 2006; 174:S13–32.

3). Kotloff RM, Blosser S, Fulda GJ, Malinoski D, Ahya VN, Angel L, et al. 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; 43:1291–325.

4). A definition of irreversible coma. Report of the Ad Hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. JAMA. 1968; 205:337–40.

5). Practice parameters for determining brain death in adults (summary statement). The Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1995; 45:1012–4.

6). Wijdicks EF, Varelas PN, Gronseth GS, Greer DM. American Academy of Neurology. Evidence-based guideline update: determining brain death in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2010; 74:1911–8.

7). Chiari P, Hadour G, Michel P, Piriou V, Rodriguez C, Budat C, et al. Biphasic response after brain death induction: prominent part of catecholamines release in this phenomenon. J Heart Lung Transplant. 2000; 19:675–82.

8). Novitzky D. Detrimental effects of brain death on the potential organ donor. Transplant Proc. 1997; 29:3770–2.

9). D'Amico TA, Meyers CH, Koutlas TC, Peterseim DS, Sabiston DC Jr., Van Trigt P, et al. Desensitization of myocardial beta-adrenergic receptors and deterioration of left ventricular function after brain death. J Thorac Cardiovasc Surg. 1995; 110:746–51.

10). Novitzky D, Cooper DK, Rosendale JD, Kauffman HM. Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation. 2006; 82:1396–401.

11). Wheeldon DR, Potter CD, Oduro A, Wallwork J, Large SR. Transforming the "unacceptable" donor: outcomes from the adoption of a standardized donor management technique. J Heart Lung Transplant. 1995; 14:734–42.

12). Van Bakel AB. The cardiac transplant donor: identification, assessment, and management. Am J Med Sci. 1997; 314:153–63.

13). Sutherland AJ, Ware RS, Winterford C, Fraser JF. The endothelin axis and gelatinase activity in alveolar macrophages after brainstem death injury: a pilot study. J Heart Lung Transplant. 2007; 26:1040–7.

14). 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; 28:111. e1–7.

15). Legrand M, Dupuis C, Simon C, Gayat E, Mateo J, Lukaszewicz AC, et al. Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study. Crit Care. 2013; 17:R278.

16). Gramm HJ, Meinhold H, Bickel U, Zimmermann J, von Hammerstein B, Keller F, et al. Acute endocrine failure after brain death? Transplantation. 1992; 54:851–7.

17). Howlett TA, Keogh AM, Perry L, Touzel R, Rees LH. Anterior and posterior pituitary function in brainstem-dead donors. A possible role for hormonal replacement therapy. Transplantation. 1989; 47:828–34.

18). Damman J, Daha MR, van Son WJ, Leuvenink HG, Ploeg RJ, Seelen MA. Crosstalk between complement and Toll-like receptor activation in relation to donor brain death and renal ischemia-reperfusion injury. Am J Transplant. 2011; 11:660–9.

19). Wood KE, Becker BN, McCartney JG, D'Alessandro AM, Coursin DB. Care of the potential organ donor. N Engl J Med. 2004; 351:2730–9.

20). Rosengard BR, Feng S, Alfrey EJ, Zaroff JG, Emond JC, Henry ML, et al. Report of the Crystal City meeting to maximize the use of organs recovered from the cadaver donor. Am J Transplant. 2002; 2:701–11.

21). 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; 71:990–5.

22). 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; 40:2773–80.

23). 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; 149:969–75.

24). Cittanova ML, Leblanc I, Legendre C, Mouquet C, Riou B, Coriat P. Effect of hydroxyethylstarch in brain-dead kidney donors on renal function in kidney-transplant recipients. Lancet. 1996; 348:1620–2.

25). Blasco V, Leone M, Antonini F, Geissler A, Albanè se J, Martin C. Comparison of the novel hydroxyethylstarch 130/0.4 and hydroxyethylstarch 200/0.6 in brain-dead donor resuscitation on renal function after transplantation. Br J Anaesth. 2008; 100:504–8.

26). Hé bert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999; 340:409–17.

27). Schnuelle P, Yard BA, Braun C, Dominguez-Fernandez E, Schaub M, Birck R, et al. Impact of donor dopamine on immediate graft function after kidney transplantation. Am J Transplantat. 2004; 4:419–26.

28). 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; 302:1067–75.

29). 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; 58:1768–77.

30). De Backer D, Biston P, Devriendt J, Madl C, Chochrad D, Aldecoa C, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med. 2010; 362:779–89.

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

32). Stoica SC, Satchithananda DK, White PA, Parameshwar J, Redington AN, Large SR. Noradrenaline use in the human donor and relationship with load-independent right ventricular contractility. Transplantation. 2004; 78:1193–7.

33). 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; 30:1771–80.

34). Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014; 370:1583–93.

35). Audibert G, Charpentier C, Seguin-Devaux C, Charretier PA, Gregoire H, Devaux Y, et al. Improvement of donor myocardial function after treatment of autonomic storm during brain death. Transplantation. 2006; 82:1031–6.

36). 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; 304:2620–7.

37). 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; 160:265–71.

38). 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; 17:423–9.

39). McElhinney DB, Khan JH, Babcock WD, Hall TS. Thoracic organ donor characteristics associated with successful lung procurement. Clin Transplant. 2001; 15:68–71.

40). Prowle JR, Kirwan CJ, Bellomo R. Fluid management for the prevention and attenuation of acute kidney injury. Nat Rev Nephrol. 2014; 10:37–47.

41). Marik PE, Cavallazzi R. Does the central venous pressure predict fluid responsiveness? An updated metaanalysis and a plea for some common sense. Crit Care Med. 2013; 41:1774–81.

42). Boyd JH, Forbes J, Nakada TA, Walley KR, Russell JA. Fluid resuscitation in septic shock: a positive fluid balance and elevated central venous pressure are associated with increased mortality. Crit Care Med. 2011; 39:259–65.

43). Miñ ambres E, Rodrigo E, Ballesteros MA, Llorca J, Ruiz JC, Fernandez-Fresnedo G, et al. Impact of restrictive fluid balance focused to increase lung procurement on renal function after kidney transplantation. Nephrol Dial Transplant. 2010; 25:2352–6.

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

45). Blasco V, Leone M, Bouvenot J, Geissler A, Albanè se J, Martin C. Impact of intensive care on renal function before graft harvest: results of a monocentric study. Crit Care. 2007; 11:R103.

46). Figueras J, Busquets J, Grande L, Jaurrieta E, Perez-Ferreiroa J, Mir J, et al. The deleterious effect of donor high plasma sodium and extended preservation in liver transplantation. A multivariate analysis. Transplantation. 1996; 61:410–3.

47). Totsuka E, Fung U, Hakamada K, Tanaka M, Takahashi K, Nakai M, et al. Analysis of clinical variables of donors and recipients with respect to short-term graft outcome in human liver transplantation. Transplant Proc. 2004; 36:2215–8.

48). Gonzá lez FX, Rimola A, Grande L, Antolin M, Garcia-Valdecasas JC, Fuster J, et al. Predictive factors of early postoperative graft function in human liver transplantation. Hepatology. 1994; 20:565–73.

49). Shah VR. Aggressive management of multiorgan donor. Transplant Proc. 2008; 40:1087–90.

50). 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; 61:429–33. discussion 33–5.

51). Novitzky D, Cooper DK, Morrell D, Isaacs S. Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy. Transplantation. 1988; 45:32–6.

52). Smith M. Physiologic changes during brain stem death–lessons for management of the organ donor. J Heart Lung Transplant. 2004; 23(9 Suppl):S217–22.

53). Novitzky D, Wicomb WN, Cooper DK, Tjaalgard MA. Improved cardiac function following hormonal therapy in brain dead pigs: relevance to organ donation. Cryobiology. 1987; 24:1–10.

54). Rosendale JD, Kauffman HM, McBride MA, Chabalewski FL, Zaroff JG, Garrity ER, et al. Hormonal resuscitation yields more transplanted hearts, with improved early function. Transplantation. 2003; 75:1336–41.

55). 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.

56). Holmes CL, Patel BM, Russell JA, Walley KR. Physiology of vasopressin relevant to management of septic shock. Chest. 2001; 120:989–1002.

57). Weiss S, Kotsch K, Francuski M, Reutzel-Selke A, Mantouva-lou L, Klemz R, et al. Brain death activates donor organs and is associated with a worse I/R injury after liver transplantation. Am J Transplant. 2007; 7:1584–93.

58). Kotsch K, Ulrich F, Reutzel-Selke A, Pascher A, Faber W, Warnick P, et al. Methylprednisolone therapy in deceased donors reduces inflammation in the donor liver and improves outcome after liver transplantation: a prospective randomized controlled trial. Ann Surg. 2008; 248:1042–50.

59). Venkateswaran RV, Dronavalli V, Lambert PA, Steeds RP, Wilson IC, Thompson RD, et al. The proinflammatory environment in potential heart and lung donors: prevalence and impact of donor management and hormonal therapy. Transplantation. 2009; 88:582–8.

60). 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:R158.

61). Cooper DK, Novitzky D, Wicomb WN. The pathophysiological effects of brain death on potential donor organs, with particular reference to the heart. Ann R Coll Surg Engl. 1989; 71:261–6.

62). 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; 83:41–7.

63). Masson F, Thicoï pe M, Latapie MJ, Maurette P. Thyroid function in brain-dead donors. Transpl Int. 1990; 3:226–33.

64). Rosendale JD, Kauffman HM, McBride MA, Chabalewski FL, Zaroff JG, Garrity ER, et al. Aggressive pharmacologic donor management results in more transplanted organs. Transplantation. 2003; 75:482–7.

65). Salim A, Martin M, Brown C, Inaba K, Roth B, Hadjizacharia P, et al. Using thyroid hormone in brain-dead donors to maximize the number of organs available for transplantation. Clin Transplant. 2007; 21:405–9.

66). Salim A, Vassiliu P, Velmahos GC, Sava J, Murray JA, Belzberg H, et al. The role of thyroid hormone administration in potential organ donors. Arch Surg. 2001; 136:1377–80.

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

68). Novitzky D, Mi Z, Sun Q, Collins JF, Cooper DK. Thyroid hormone therapy in the management of 63,593 brain-dead organ donors: a retrospective analysis. Transplantation. 2014; 98:1119–27.

69). 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; 110:333–41.

70). 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; 215:217–30.

71). NICE-SUGAR Study Investigators; Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009; 360:1283–97.

72). 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; 373:405–14.

73). Kootstra G, Daemen JH, Oomen AP. Categories of non-heart-beating donors. Transplant Proc. 1995; 27:2893–4.

74). Gravel MT, Arenas JD, Chenault R 2nd, Magee JC, Rudich S, Maraschio M, et al. Kidney transplantation from organ donors following cardiopulmonary death using extracorporeal membrane oxygenation support. Ann Transplant. 2004; 9:57–8.

75). Fondevila C, Hessheimer AJ, Flores E, Ruiz A, Mestres N, Calatayud D, et al. Applicability and results of Maastricht type 2 donation after cardiac death liver transplantation. Am J Transplant. 2012; 12:162–70.

76). Bernat JL, Capron AM, Bleck TP, Blosser S, Bratton SL, Childress JF, et al. The circulatory-respiratory determination of death in organ donation. Crit Care Med. 2010; 38:963–70.

77). Migliaccio ML, Zagli G, Cianchi G, Lazzeri C, Bonizzoli M, Cecchi A, et al. Extracorporeal membrane oxygenation in brain-death organ and tissues donors: a single-centre experience. Br J Anaesth. 2013; 111:673–4.