Professional Documents
Culture Documents
Review Article
Suboptimal, unstandardized critical care manage- delivered to potential organ donors, so as to reduce
ment of potential organ donors is one of the organ shortages, improve organ procurement, and
reasons for the demand for donor organs exceeding promote graft survival. However, ensuring the
their supply. The progression from brain death to quality of donor organs is not only a matter of a
somatic death results in the loss of 10–20% of systemic treatment approach, but also a matter of
potential donors (1, 2). The pathophysiological time: instability of the condition of the potential
changes following brain death entail a high inci- donor increases in proportion to the length of time
dence of complications jeopardizing potentially between the declaration of brain death and organ
transplantable organs. Adverse events include car- procurement (3). In this review, we present the
diovascular changes, endocrine and metabolic current guidelines at our department, which are
disturbances, and disruption of internal homeosta- optimized based on available literature.
sis. Brain death also upregulates the release of
pro-inflammatory molecules. In clinical practice,
Pathophysiological changes associated with brain
hypotension, diabetes insipidus, relative hypother-
death
mia, and hypernatremia are more common than
disseminated intravascular coagulation, cardiac Frequently, brain death as a result of increased
arrhythmias, pulmonary edema, acute lung injury, intracranial pressure after severe brain injury
and metabolic acidosis. Strategies for the manage- follows a similar pattern of rostral–caudal cerebral
ment of organ donors exist and consist of the herniation leading to brain stem ischemia. Mean
normalization of donor physiology. This has arterial pressure rises in an effort to maintain
resulted in efforts to improve the critical care cerebral perfusion pressure. Initially, an ischemic
2
Critical care management of potential organ donors
3
Dictus et al.
4
Critical care management of potential organ donors
Renal considerations
Brain death provokes both immunological and
non-immunological damage to the kidneys, which
may increase the rate of delayed allograft function,
the risk of acute and chronic rejection, and the
incidence of renal allograft nephropathy, and may
decrease recipient survival (14, 37, 39, 45–47).
Recent literature reports a beneficial immunomod-
ulatory effect of catecholamines on donor kidney
function (40, 48). However, vasopressor therapy
with high doses of dopamine (> 10 lg/kg/min) or
norepinephrine may compromise organ perfusion
because of their vasoconstrictive mechanism of
action, thus increasing the incidence of acute
tubular necrosis and allograft failure (23, 49). On
the other hand, epinephrine has been reported to
improve systemic hemodynamic function and to
maintain renal perfusion (23, 50–52). Although
there is no consensus on the specific combination
of catecholamines, combination therapy has been
associated with a reduction in the rates of acute
Fig. 2. Standardized critical care management of potential
organ donors in our center. MAP, mean arterial blood pres-
rejection after renal transplantation and with
sure; CVP, central venous pressure; LVEF, left ventricular improved graft survival (23, 49, 53–55). Arginine–
ejection fraction; T3, triiodothyronine. vasopressin, that has been shown to reduce the
need for vasoactive drugs in potential organ
oxygen pressure (PaO2) with lowest fraction of donors, does not seem to exert deleterious short-
inspiratory oxygen (39). The two most correctable term or long-term effects on renal graft function in
causes of hypoxemia that preclude recovery of the recipient (23) and therefore appears to be a
lungs for transplantation are atelectasis and exces- suitable alternative if catecholamines are to be
sive fluid replacement. To prevent atelectasis, to avoided. Furthermore, to ensure adequate renal
remove secretions and foreign bodies, and to perfusion, colloids such as hydroxyethyl starch
isolate potential pathogens, bronchoscopy should may also be used in recommended dosages, refer-
be performed in all donors. This also helps to ring to recent studies that failed to show any
choose the best antibiotic therapy in donor and impairment in immediate renal graft recipients as it
recipient, which is of extreme importance because was formerly thought (19, 56). Because autoregu-
bronchopneumonia is one of the most common lation of renal blood flow and glomerular filtra-
reasons for rejecting lungs (37, 42). High-dose tion declines below a systolic blood pressure of
5
Dictus et al.
6
Critical care management of potential organ donors
death (29, 76–78), treatment with corticosteroids because of central diabetes insipidus, excessive
has been proven to be beneficial in potential organ fluid replacement to ensure hemodynamic stability
donors both because of their immunomodulatory or the aftermath of osmotic diuresis with mannitol
effects and their stabilization of systemic vascular for the treatment of increased intracranial pressure.
resistance with catecholamine-sparing effects (34). Because elevated sodium levels have been associ-
The optimal dose, however, remains uncertain. ated with higher rates of primary graft failure (36,
Hyperglycemia is another common event after 69), it is essential to compensate hypernatremia by
brain death and arises from massive catecholamine infusing 5% dextrose solution in water or half
release, infusion of dextrose-containing fluids, and normal saline (0.45%) as well as treating potential
peripheral insulin resistance. Because hyperglyce- causes, e.g., hormonal replacement with arginine–
mic damage to pancreatic beta cells is linked with vasopressin or desmopressin. Besides, maintenance
graft dysfunction in pancreatic transplants (16, 79), of metabolic and respiratory acid–base balance has
strict control of blood glucose levels by means of to be considered in potential organ donors. Respi-
an insulin infusion is essential to achieve euglyce- ratory alkalosis following hyperventilation during
mia (80–150 mg/dL) (23). the treatment of increased intracranial pressure
worsens tissue oxygenation so that normocapnia
should be achieved. On the other hand, metabolic
Supportive critical care acidosis most likely resulting from an increase in
metabolic activity because of a lack of T3 in
Hypothermia
potential organ donors (81) may worsen cardiac
Loss of hypothalamic thermoregulation following function necessitating correction with trometamol
cerebral herniation, peripheral vasodilatation be- or sodium bicarbonate (16).
cause of the deactivation of sympathetic tone
resulting in increased heat emission and reduction
Conclusion
in metabolic activity lead to the inability of keeping
body temperature within the physiological range In summary, caring for a brain dead potential
(poikilothermia) and, most frequently, to hypo- organ donor requires a shift in critical care
thermia (80). Because hypothermia may cause therapy from the extensive treatment of increased
adverse events such as cardiac dysfunction, ar- intracranial pressure toward strategies to main-
rhythmias, deterioration of microcirculation and tain donor organ function. A systematic and
oxygen consumption, coagulopathy, or cold-in- optimized critical care management (as summar-
duced diuresis, core body temperature should be ized in fig. 2) increases not only the number, but
maintained at ‡ 35C, e.g., by means of convective also the quality of suitable organs, aiming at an
warming blankets or warming of fluids. optimal outcome for the recipients.
7
Dictus et al.
7. Tuttle-Newhall JE, Collins BH, Kuo PC, Schoeder for characterization and a guide to therapy. J Heart Lung
R. Organ donation and treatment of the multi-organ do- Transplant 1995: 14: 59.
nor. Curr Probl Surg 2003: 40: 266. 26. Debaveye YA, Van den Berghe GH. Is there still a place
8. Shivarlkar B, Van Loon J, Wieland W et al. Variable for dopamine in the modern intensive care unit? Anesth
effects of explosive or gradual increase of intracranial Analg 2004: 98: 461.
pressure on myocardial structure and function. Circulation 27. Marik PE, Mohedin M. The contrasting effects of
1993: 87: 230. dopamine and norepinephrine on systemic and splanchnic
9. Carber C, Manyalich M, Valero R, Garcia-Fages oxygen utilization in hyperdynamic sepsis. JAMA 1994:
LC. Timing used in the different phases of the organ 272: 1354.
procurement process. Transplant Proc 1992: 24: 22. 28. Tilney NL, Paz D, Ames J, Gasser M, Laskowski I,
10. Kosieradzki M, Kuczynska J, Piwowarska J et al. Hancock WW. Ischemia-reperfusion injury. Transplant
Prognostic significance injury occurring in the kidney do- Proc 2001: 33: 843.
nor. Transplantation 2003: 75: 1221. 29. Amado JA, Lopez-Espadas F, Vazquez-Barquero A
11. Lagiewska B, Pacholczyk M, Szostek M, Walaszew- et al. Blood levels of cytokines in brain-dead patients:
ski J, Rowinski W. Hemodynamic and metabolic distur- relationship with circulating hormones and acute-phase
bances observed in brain-dead organ donors. Transplant reactants. Metabolism 1995: 44: 812.
Proc 1996: 28: 165. 30. Stangl M, Zerkaulen T, Theodorakis J et al. Influence
12. Finfer S, Bohn D, Colpitts D, Cox P, Fleming F, of brain death on cytokine release in organ donors and
Barker G. Intensive care management of pediatric organ renal transplants. Transplant Proc 2001: 33: 1284.
donors and its effect on post transplant organ function. 31. Iwai A, Sakano T, Uenishi M, Sugimoto H, Yoshioko
Intensive Care Med 1996: 22: 1424. T, Sugimoto T. Effects of vasopressin and cathecholam-
13. Van der Hoeven JA, Ter Horst GJ, Molema G et al. ines on the maintenance of circulatory stability in brain-
Effects of brain death and hemodynamic status on func- dead patients. Transplantation 1989: 48: 613.
tion and immunologic activation of the potential donor 32. Katz K, Lawler J, Wax J, OÕConnor R, Nadkarni V.
liver in the rat. Ann Surg 2000: 232: 804. Vasopressin pressor effects in critically ill children during
14. Kusaka M, Pratschke J, Wilhelm MJ et al. Activation evaluation for brain death and organ recovery. Resusci-
of inflammatory mediators in rat renal isografts by donor tation 2000: 47: 33.
brain death. Transplantation 2000: 69: 405. 33. Hunt SA, Baldwin J, Baumgartner W et al. Cardio-
15. Hefty TR, Cotterell LW, Fraser SC, Goodnight SH, vascular management of a potential heart donor: a state-
Hatch TR. Disseminated intravascular coagulation in ment from the transplantation committee of the American
cadaveric organ donors. Incidence and effect on renal College of Cardiology. Crit Care Med 1996: 24: 1599.
transplantation. Transplantation 1993: 55: 442. 34. Marik PE, Varon J, Trask T. Management of head
16. Hoemme R, Neeser G. Organ donation. Anaesthesist trauma. Chest 2002: 122: 699.
2007: 56: 1291. 35. Howlett TA, Keogh AM, Perry L, Touzel R, Rees
17. Power BM, Van Heerden PV. The physiological changes LH. Anterior and posterior pituitary function in brain
associated with brain death-current concepts and implan- stem dead donors. A possible role for hormonal replace-
tations for treatment of the brain dead organ donor. ment therapy. Transplantation 1989: 47: 828.
Anaesth Intensive Care 1995: 23: 26. 36. Gramm HJ, Meinhold H, Bickel U et al. Acute endo-
18. Zaroff JG, Rosengard BR, Armstrong WF et al. crine failure after brain death? Transplantation 1992: 54:
Consensus conference report: maximizing use of organs 851.
recovered from the cadaver donor: cardiac recommenda- 37. Shah VR. Aggressive management of multiorgan donor.
tions March 28–29 2001, Crystal City, Va. Circulation Transplant Proc 2008: 40: 1087.
2002: 106: 836. 38. Avlonitis VS, Fisher AJ, Kirby JA, Dark JH. Pulmo-
19. Deman A, Peeters P, Sennesael J. Hydroxyethyl starch nary transplantation: the role of brain death in donor lung
does not impair immediate renal function in kidney injury. Transplantation 2003: 75: 1928.
transplant recipients: a retrospective, multicenter analysis. 39. Kutsogiannis DJ, Pagliarello G, Doig C, Ross H,
Nephrol Dial Transplant 1999: 14: 1517. Shemie SD. Medical management to optimize donor or-
20. Reilly PM, Grossman M, Rosengard BRE. Lung gan potential: review of the literature. Can J Anaesth 2006:
procurement from solid organ donors: role of fluid 53: 820.
resuscitation in procurement failures. Chest 1996: 110: 40. Wood KE, Coursin DB. Intensivists and organ donor
222S. management. Curr Opin Anaesthesiol 2007: 20: 97.
21. Rosengard BR, Feng S, Alfrey EJ et al. Report of the 41. Pennefather SH, Bullock RE, Dark JH. The effect of
crystal city meeting to maximize the use of organs recov- fluid therapy on alveolar arterial oxygen gradient in brain
ered from the cadaver donor. Am J Transplant 2002: 2: dead organ donors. Transplantation 1993: 56: 1418.
701. 42. Aziz TM, El-Gamel A, Saad RA, Migliore M, Campbell
22. Hevesi ZG, Lopukhin SY, Angelini G, Coursin DB. CS, Yonan NA. Pulmonary vein gas analysis for assessing
Supportive care after brain death for the donor candidate. donor lung function. Ann Thorac Surg 2002: 73: 1599.
Int Anesthesiol Clin 2006: 44: 21. 43. Gabbay E, Williams TJ, Griffiths AP et al. Maximizing
23. Wood KE, Becker BN, Mccartney JG, DÕAlessandro the utilization of donor organ offered for lung transplan-
AM, Coursin DB. Care of the potential organ donor. tation. Am J Respir Crit Care Med 1999: 160: 265.
NEJM 2004: 351: 2730. 44. Follette D, Rudich S, Bonacci C, Allen R, Hoso A,
24. Wheeldom DR, Potter CD, Oduro A, Wallwork J, Albertson T. Importance of an aggressive multidisci-
Large SR. Transforming the unacceptable donor: out- plinary management approach to optimize lung donor
comes from the adoption of a standardized donor man- procurement. Transplantation Proc 1999: 31: 169.
agement technique. J Heart Lung Transplant 1995: 14: 734. 45. Tanaka N. Radiologic-pathologic correlation of experi-
25. Potter CD, Wheeldon DR, Wallwork J. Functional mental bleomycin-induced pneumonitis. Nippon Iqaku
assessment and management of heart donors: a rationale Hoshasen Gakkai Zasshi 1993: 53: 1392.
8
Critical care management of potential organ donors
46. Wilheim S, Maze M. Controversial issues in adult and 64. Clavien PA, Harvey PR, Strasberg SM. Preservation
paediatric ambulatory anaesthesia: is there a role for and reperfusion injuries in liver allografts. An overview
alpha-2 agonist in conscious sedation in adults and and synthesis of current studies. Transplantation 1992: 53:
paediatric ambulatory surgical practice. Curr Opin Ana- 957.
esthesiol 2000: 13: 619. 65. Brokelman W, Stel AL, Ploeg RJ. Risk factors for
47. Postema S, Pattynama PM, van Rijswijk CS, Trimbos primary dysfunction after liver transplantation in the
JB. Cervical carcinoma: can dynamic contrast enhanced university of Wisconsin solution era. Transplant Proc
MR imaging help predict tumor aggressiveness. Radiology 1999: 31: 2087.
1999: 210: 217. 66. Porte RJ, Ploeg RJ, Hansen B et al. Lonh term graft
48. De Boer ML, Hu J, Kalvakolanu DV, Hasdav JD, survival after liver transplantation in the UW era: late ef-
Cross AS. INF gamma inhibits lipopolysaccharide-in- fects of cold ischemia and primary dysfunction. European
duced interleukin 1 beta in primary murine macrophages Multicenter Study Group. Transpl Int 1998: 11(Suppl. 1):
via a Stat 1 dependent pathway. J Interferon Cytokine Res S164.
2001: 21: 485. 67. Figueras J, Busquets J, Grande L et al. The deleterious
49. Van der Wounde FJ, Ferrario F. Renal involvement in effect of donor high plasma sodium and extrended pres-
ANCA associated systemic vasculitis. J Nephrol 1999: 12: ervation in liver transplantation. A multivariate analysis.
105. Transplantation 1996: 61: 410.
50. Itoh M, Kuroda K. Impressions on 11th international 68. Gonzalez FX, Rimola A, Grande L et al. Predictive
conference on Nagative Strand Viruses. Uirusu 2000: 50: factors of early postoperative graft function in human liver
319. transplantation. Hepatology 1994: 20: 565.
51. Zivna H, Zivny P, Navratil P et al. The role of cytokines 69. Totsuka E, Dodson F, Urakami A et al. Influence of
and antioxidant status in graft quality prediction. Trans- high donor serum sodium levels on early postoperative
plant Proc 1999: 31: 2094. graft function in human liver transplantation: effect of
52. Nagareda T, Kinoshita Y, Tanaka A et al. Clinicopa- correction of donor hypernatremia. Kidney Transpl Surg
thology of kidneys from brain dead patients treated with 1999: 5: 421.
vasopressin and epinephrine. Kidney Int 1993: 43: 1363. 70. Sazontseva IE, Kozlov IA, Moisuc YG, Ermolenko
53. Pratschke J, Wilhelm MJ, Kusaka M et al. Accelerated AE, Afonin VV, Ilnitskiy VV. Hormonal response to
rejection of renal allograft from brain dead donors. Ann brain death. Transplant Proc 1991: 23: 2467.
Surg 2000: 232: 263. 71. Holmes CL, Patel BM, Russell JA, Walley KR.
54. Schnuelle P, Berger S, de Boer J, Persijn G, van der Physiology of vasopressin relevant to management of
Wounde FJ. Effects of catecholamine application to brain septic shock. Chest 2001: 120: 989.
dead donors on graft survival in solid organ transplanta- 72. Novitzky D, Cooper DK, Reichart B. Hemodynamic
tion. Transplantation 2001: 72: 455. and metabolic responses to hormonal therapy in brain
55. Schnuelle P, Lorenzo D, Mueller A, Trede M, Van dead potential organ donors. Transplantation 1987: 43:
der wounde FJ. Donor catecholamine use reduces acute 852.
allograft rejection and improves graft survival after 73. Rosendale JD, Kauffman HM, McBride MA et al.
cadaveric renal transplantation. Kidney Int 1999: 56: 738. Aggressive pharmacologic donor management results in
56. Singer AC, Wong CS, Crowley DE. Differential enan- more transplanted organs. Transplantation 2003: 75:
tioselective transformation of atropisomeric polychlori- 482.
nated biphenyls by multiple bacterial strains with different 74. Jeevanandam V. Triiodothyronine: spectrum of use in
including compounds. Appl Environ Microbiol 2002: 68: heart transplantation. THYROID 1997: 7: 139.
5756. 75. Salim A, Vassiliu P, Velmahos GC et al. The role of
57. Tepel M, van der Giet M, Schwarzfeld C, Laufer U, thyroid hormone administration in potential organ do-
Liermann D, Zidek W. Prevention of radiographic con- nors. Arch Surg 2001: 136: 1377.
trast agent induced reductions in renal function by ace- 76. Pratschke J, Wilhelm MJ, Kusaka M et al. Brain death
tylcysteine. N Engl J Med 2000: 343: 180. and its influence on donor organ quality and outcome after
58. Efrati S, Dishy V, Averbukh M et al. The effect of N- transplantation. Transplantation 1999: 67: 343.
acetylcycteine on renal function, nitric oxide and oxidative 77. Birks EJ, Burton PB, Owen V et al. Elevated tumor
stress after angiography. Kidney Int 2003: 64: 2182. necrosis factor alpha and interleukin 6 in myocardium and
59. Briguori C, Manganelli F, Scarpato P et al. Acetyl- serum of malfunctioning donor hearts. Circulation 2000:
cysteine and contrast agent associated nephrotoxicity. J 102(Suppl. 3): III 52.
Am Coll Cardiol 2002: 40: 298. 78. Nijboer WN, Schuurs TA, van der Hoeven JA et al.
60. Diaz-Sandoval LJ, Kosowsky BD, Losordo DW. Ace- Effects of brain death on stress and inflammatory response
tylcysteine to prevent angiography related renal tissue in- in the human donor kidney. Transplant Proc. 2005 Jan–
jury (the APART trial). Am J Cardiol 2002: 89: 356. Feb: 37: 367–9.
61. Kay J, Chow WH, Chan TM et al. Acetylcysteine for 79. Gores PF, Gillingham KJ, Dunn DL, Moudry-Munns
prevention of acute deterioration of renal function fol- KC, Najarian JS, Sutherland DE. Donor hyperglyce-
lowing elective coronary angiography and intervention: a mia as a minor risk factor and immunologic variables as
randomized controlled trial. JAMA 2003: 289: 553. major risk factors for pancreas allograft loss in a multi-
62. Merten GJ, Burgess WP, Rittase RA, Kennedy TP. variate analysis of a single institution s experience. Ann
Prevention of contrast induced nephropathy with sodium Surg 1992: 215: 217.
bicarbonate: an evidence based protocol. Crit Pathw 80. Smith M. Physiologic changes during brain stem death
Cardiol 2004: 3: 138. lessons for management of the organ donor. J Heart Lung
63. Ploeg RJ, DÕAlessandro AM, Knechtle SJ et al. Risk Transplant 2004: 23: S217.
factoers for primary dysfunction after liver transplanta- 81. Powner DJ, Hendrich A, Lagler RG, Ng RH, Mad-
tion – a multivariate analysis. Transplantation 1993: 55: den RL. Hormonal changes in brain dead patients. Crit
807. Care Med 1990: 18: 702.