Organ Donor Critical Care: Current Standards & Management

ª 2009 John Wiley & Sons A/S.
Clin Transplant 2009: 23 (Suppl. 21): 2–9 DOI: 10.1111/j.1399-0012.2009.01102.x
Review Article
Critical care management of potential organ
donors: our current standard
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. ª 2009 John Wiley & Sons A/S.
C. Dictusa*, B. Vienenkoettera*,
M. Esmaeilzadehb, A. Unterberga
and R. Ahmadia
a
Abstract: Caring for a brain dead potential organ donor requires a shift in
critical care from the extensive treatment of increased intracranial pressure
towards strategies to maintain donor organ function. Suboptimal, unstandardized critical care management of organ donors, however, is one of
the main reasons for insufficient organ procurement. The pathophysiological changes following brain death entail a high incidence of complications
including hemodynamic instability, endocrine and metabolic disturbances,
and disruption of internal homeostasis that jeopardize potentially transplantable organs. Strategies for the management of organ donors exist and
consist of the normalization of donor physiology. This has resulted in
standardized efforts to improve the critical care delivered to potential organ
donors, increasing not only the number, but also the quality of suitable
organs and aiming at an optimal outcome for the recipients. In this review,
we discuss the pathophysiological changes associated with brain death and
present the current guidelines at our department, which are optimized based
on available literature.
Department of Neurosurgery and bDepartment
of General, Visceral and Transplantation Surgery,
University of Heidelberg, Heidelberg, Germany
Key words: brain death – donor candidate –
critical care management – standardized
treatment strategies – pathophysiological
considerations
Corresponding author: Dr. Christine Dictus, MD,
Department of Neurosurgery, University of Heidelberg, INF 400, 69120 Heidelberg, Germany.
Tel.: +49 6221 566308; fax: +49 6221 565534;
e-mail: [email protected]
*Christine Dictus and Barbara Vienenkoetter
contributed equally to this work.
Accepted for publication 12 May 2009
Suboptimal, unstandardized critical care management of potential organ donors is one of the
reasons for the demand for donor organs exceeding
their supply. The progression from brain death to
somatic death results in the loss of 10–20% of
potential donors (1, 2). The pathophysiological
changes following brain death entail a high incidence of complications jeopardizing potentially
transplantable organs. Adverse events include cardiovascular changes, endocrine and metabolic
disturbances, and disruption of internal homeostasis. Brain death also upregulates the release of
pro-inflammatory molecules. In clinical practice,
hypotension, diabetes insipidus, relative hypothermia, and hypernatremia are more common than
disseminated intravascular coagulation, cardiac
arrhythmias, pulmonary edema, acute lung injury,
and metabolic acidosis. Strategies for the management of organ donors exist and consist of the
normalization of donor physiology. This has
resulted in efforts to improve the critical care
2
delivered to potential organ donors, so as to reduce
organ shortages, improve organ procurement, and
promote graft survival. However, ensuring the
quality of donor organs is not only a matter of a
systemic treatment approach, but also a matter of
time: instability of the condition of the potential
donor increases in proportion to the length of time
between the declaration of brain death and organ
procurement (3). In this review, we present the
current guidelines at our department, which are
optimized based on available literature.
Pathophysiological changes associated with brain
death
Frequently, brain death as a result of increased
intracranial pressure after severe brain injury
follows a similar pattern of rostral–caudal cerebral
herniation leading to brain stem ischemia. Mean
arterial pressure rises in an effort to maintain
cerebral perfusion pressure. Initially, an ischemic
Critical care management of potential organ donors
mesencephalon results in parasympathetic activation clinically manifest with sinus bradycardia and
hypotension. Subsequent pontine ischemia leads to
sympathetic stimulation with superimposed hypertension (CushingÕs reflex) (4, 5). This is followed by
the ‘‘autonomic storm’’, a phase of intensive
sympathetic activity with massive catecholamine
release, which is because of ischemia of the vagal
cardiomotor nucleus in the medulla oblongata (6,
7), dramatically increasing myocardial work (8),
and jeopardizing end organ blood flow. Finally,
spinal cord sympathetic deactivation results in the
loss of vasomotor tone with subsequent vasodilatation and impaired cardiac output. Together with
vasopressin deficiency as a result of pituitary gland
ischemia and subsequent diabetes insipidus, only a
minority of potential organ donors are able to
maintain hemodynamic stability without intensified critical care therapy (9–12). However, potential
donor organs are endangered not only by ischemic
damage, but also by reperfusion injury when the
circulation is restored, leading to a generalized
inflammatory response (13, 14). Damaged or
necrotic brain tissue induces a release of plasminogen activator and thromboplastin with a risk of
disseminated intravasal coagulopathy (15). Furthermore, loss of hypothalamic–pituitary function
results in the loss of thermoregulation with
subsequent hypothermia. Together with the massive release of catecholamines during the autonomic storm, this, in turn, can cause malfunction
of platelets further deteriorating blood coagulation. A schematic overview of the pathophysiological changes associated with brain death is given
in Fig. 1.
Cardiovascular considerations
Because of the pathophysiological changes described previously, hemodynamic instability is a
major challenge in the treatment of brain dead
potential organ donors. Hypertension is a rare
event usually occurring during the phase of
cerebral herniation itself and is therefore mostly
self-limitating. In case of prolonged hypertension,
short-acting substances such as urapidil, esmolol,
or nitroprusside should be preferred (16). Hypotension, however, affects almost all patients after
brain death (3, 17), and sustained hypotension
may occur in 20 percent of donors, despite
vasoactive-drug support (3). Because hypotension
is associated with diminished blood and oxygen
supply and, subsequently, with a decrease in
donor organ function, it is essential to identify
and treat putative causes. In severely brain-damaged patients, hypotension most frequently occurs
because of hypovolemia related to traumatic
blood loss, central diabetes insipidus, or osmotic
therapy for increased intracranial pressure, but
also because of the loss of sympathetic tone
during cerebral herniation, giving rise to blunted
vasomotor reflexes, vasodilatation, and impaired
cardiac contractility. Therefore, a systematic
approach is needed to achieve hemodynamic
stability aiming at a mean arterial pressure
(MAP) of ‡ 60 mmHg, a central venous pressure
(CVP) of 6–10 mmHg, a urinary output of
‡ 1 mL/kg/h, and a left ventricular ejection fraction (LVEF) of ‡ 45% as advocated by the
Crystal City Consensus Conference (18) and the
United Network for Organ Sharing (UNOS).
Baseline monitoring therefore should include
arterial and central venous catheterization, complemented by repeated echocardiography if heart
donation is considered. The initial treatment step
consists in aggressive fluid replacement, which is
usually performed with cristalloids such as lactated RingerÕs solution, normal (0.9%), or half
normal (0.45%) saline solutions. In view of recent
studies, hydroxyethyl starch can also be safely
applied with respect to renal graft function to
keep intravascular volume and colloid oncotic
pressure within physiological ranges (19). Besides,
in potential lung donors where a minimally
positive fluid balance is associated with higher
rates of lung procurement (20), colloid solutions
are suitable to minimize the accumulation of
pulmonary edema (21). In contrast, maintenance
of kidney graft function requires aggressive volume replacement. Blood transfusion should be
considered if the hemoglobin concentration is
below 10 g/dL, or the hematocrit is below 30%
(4, 18).
If thresholds of hemodynamic stability are not
achieved despite fluid resuscitation, extensive hemodynamic monitoring such as pulmonary artery
catheter, echocardiography, or new devices to
measure cardiac output (Pulscontour Continous
Cardiac Output, PiCCO, PULSION Medical
Systems, Munich, Germany) should be applied
(22–25) to assess right- and left-sided cardiac filling
pressures, cardiac output, and systemic vascular
resistance (SVR). Under these circumstances, the
administration of vasoactive drugs is indicated. In
the past, dopamine has been the catecholamine of
choice in doses of £ 10 lg/kg/min, but more
recent studies have failed to support its formerly
attributed beneficial effect on renal or hepatosplanchnic circulation (26, 27). Whenever hemodynamic stabilization requires dopamine doses of
more than 10 lg/kg/min, addition of another
inotrope such as norepinephrine or epinephrine is
3
Dictus et al.
Fig. 1. Pathophysiological changes associated with brain death.
recommended. Besides, catecholamines appear to
have distinct immunomodulatory effects that may
reduce inflammatory processes associated with
brain death (28–30). However, indication for
inotropes should be carefully thought over because
intensive application of b-agonists can impair graft
function of donor hearts by downregulation of breceptors. In this context, there has been a shift in
vasoactive-drug therapy from catecholamines to
arginine–vasopressin, which is usually applied for
the treatment of central diabetes insipidus because
of its antidiuretic effect but which, because of its
additional vasopressor function, has also demonstrated a significant catecholamine-sparing effect
without impairment of graft function (31, 32), and
its early use in potential organ donors has been
recommended by the American College of Cardiology (26, 33). Administration of hydrocortisone at
a dose of 10 mg/h has been shown to enhance
vascular reactivity in critically ill patients (34) and
therefore appears to be another feasible option to
spare catecholamines.
Arrhythmias, another hemodynamic challenge
in potential organ donors, are mainly attributable
to brain stem ischemia and the myocardial injury
caused by the autonomic storm during cerebral
herniation and are therefore highly resistant to
antiarrhythmic treatment (3, 35, 36). Ventricular
arrhythmias are best treated by lidocaine or
amiodarone, supraventricular arrhythmias by ami-
4
odarone (23). In bradyarrhythmias, anticholinergic
drugs such as atropine are not effective because of
the vagal break down during brain herniation;
rather, administration of isoproterenol or epinephrine is recommended (23).
Pulmonal considerations
Neurogenic pulmonary edema, pneumonia, and
intense inflammatory responses make successful
lung procurement in brain dead potential organ
donors challenging (37, 38). Critical care management in case of lung donation is very complex
because all components of the hemodynamic
model are affected. In this case, the American
College of Cardiology has recommended a systolic
blood pressure of 90–140 mmHg, a CVP of
8–12 mmHg, or a pulmonary capillary wedge
pressure of 12–14 mmHg (33, 39). Often, it is
necessary to take into consideration the antagonistic competing organ interests related to fluid
resuscitation. A minimal volume strategy limits the
development of extravascular lung water following
brain-death-associated permeability changes and
preserves the crucial PaO2/FiO2 gradient of at least
300 mmHg (40, 41). Recommendations for the
mechanical ventilation are a tidal volume of 10–
12 mL/kg and a positive end-expiratory pressure
(PEEP) of 5 cm H2O as well as a static airway
pressure of ‡ 30 cm H2O to achieve highest arterial
Critical care management of potential organ donors
corticosteroids and the use of colloids have also
shown benefits in the management of lung donors.
Previously, only ideal lungs were transplanted into
ideal recipients, but by reason of the number of
deaths among patients on the waiting list for lung
transplants, this approach has been challenged.
Multiple authors have reported that recipients
outcomes with less-than-ideal or ‘‘marginal’’ lungs
are equivalent to the outcomes with ideal lungs. In
these studies, aggressive pulmonary management,
including strict regulation of ventilatory settings,
moderate use of PEEP, frequent suctioning, inhalation of albuterol, use of bronchoscopy, a minimally positive fluid balance, and use of antibiotics
were the key components that enabled the transplantation of marginal lungs with successful
outcomes (43, 44).
Renal considerations
Fig. 2. Standardized critical care management of potential
organ donors in our center. MAP, mean arterial blood pressure; CVP, central venous pressure; LVEF, left ventricular
ejection fraction; T3, triiodothyronine.
oxygen pressure (PaO2) with lowest fraction of
inspiratory oxygen (39). The two most correctable
causes of hypoxemia that preclude recovery of
lungs for transplantation are atelectasis and excessive fluid replacement. To prevent atelectasis, to
remove secretions and foreign bodies, and to
isolate potential pathogens, bronchoscopy should
be performed in all donors. This also helps to
choose the best antibiotic therapy in donor and
recipient, which is of extreme importance because
bronchopneumonia is one of the most common
reasons for rejecting lungs (37, 42). High-dose
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 immunomodulatory 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
rejection after renal transplantation and with
improved graft survival (23, 49, 53–55). Arginine–
vasopressin, that has been shown to reduce the
need for vasoactive drugs in potential organ
donors, does not seem to exert deleterious shortterm or long-term effects on renal graft function in
the recipient (23) and therefore appears to be a
suitable alternative if catecholamines are to be
avoided. Furthermore, to ensure adequate renal
perfusion, colloids such as hydroxyethyl starch
may also be used in recommended dosages, referring to recent studies that failed to show any
impairment in immediate renal graft recipients as it
was formerly thought (19, 56). Because autoregulation of renal blood flow and glomerular filtration declines below a systolic blood pressure of
5
Dictus et al.
80–90 mmHg, timely hemodynamic stabilization of
potential donors is important to maintain adequate
organ perfusion and diuresis. If urine output
remains < 1 mL/kg/h after optimized hemodynamic management, diuretics such as furosemide
or mannitol are used. Nephrotoxic drugs should be
avoided, and corticosteroids are recommended to
diminish immunological damage (14, 37). In case
an angiography is performed, it is recommended to
use acetylcysteine and bicarbonate to prevent the
development of contrast nephropathy (39, 57–62).
Hepatic considerations
The liver seems to tolerate long periods of hypoperfusion because of its large physiological reserve.
Furthermore, the immunological response is weak
as it is a tolerogenic organ. Nevertheless, the
inflammatory processes related to brain death and
reperfusion injury to the liver lead to poor initial
function of liver allografts (37, 39, 63–66). Independently associated with an increased rate of
recipient death and retransplantation are ABO
incompatibility, high donor serum sodium concentration (> 155 mM), longer cold ischemia time as
well as large platelet transfusions during surgery
and prolonged recipient prothrombin time (37, 39,
64, 67, 68). Presumably, high donor serum sodium
concentrations promote the accumulation of idiogenic osmoles within the liver cells, which, after
having been transplanted into recipients with
relatively normal sodium levels, promote intracellular water accumulation, cell lysis, and death. By
all means, correcting the donor serum sodium level
below 155 mM, keeping the CVP between 8 and
10 mmHg, using a low PEEP to prevent hepatic
congestion and restoring liver glycogen stores with
adequate nutrition decreases the incidence of liver
allograft loss (37, 39, 69).
Endocrinological considerations
Dysfunction of the posterior pituitary gland with
low to undetectable levels of vasopressin occurs in
up to 90% of adult and pediatric organ donors (7,
12, 35, 36, 70) and commonly results in central
diabetes insipidus clinically manifest with polyuria
(urinary output > 300 mL/h), serum sodium concentration > 150 mM, urine sodium concentration < 20 mM, serum osmolarity > 310 mosM,
urine osmolarity > 300 mosM, and a specific
urinary weight of < 1005. Diabetes insipidus is
essential to treat because it has been linked with
hemodynamic instability in organ donors (11, 12).
Adequate treatment consists of volume replacement, and half normal saline solution (0.45%) or
6
5% solution of dextrose in water should be
preferred to decrease serum sodium levels (16,
23), because hypernatremia in organ donors has
been associated with impaired graft function,
especially after liver transplantation (69). Moreover, one has to be aware of other causes of
polyuria such as previous osmotic therapy for
increased intracranial pressure, hyperglycemia or
diuretic agents. Compensation of arginine–vasopressin deficiency in brain dead organ donors by
arginine–vasopressin or 1-desamino-8-d-arginine–
vasopressin (DDAVP; desmopressin) alone or in
combination is well accepted. Because of the
combined vasopressor and antidiuretic effect of
arginine–vasopressin, it is suitable for both hormone replacement therapy and restoration of
hemodynamic stability; however, the use of arginine–vasopressin at doses greater than 0.04 U/min
may cause coronary, renal, and splanchnic vasoconstriction jeopardizing donor organ function
(71). Desmopressin has an advantageous pharmacological profile because it specifically acts on the
V2-vasopressin receptors, therefore exerting predominantly antidiuretic effects, and has an extended duration of action (6–20 h) (41).
Deficiency of hormones regulated by the anterior
pituitary gland including T3 (triiodothyronine), T4
(thyroxine), thyroid stimulation hormone, adrenocorticotropic hormone, and human growth hormone has been described inconsistently (72). There
are hints from a large retrospective analysis of the
Organ Procurement and Transplantation Network
OPTN/UNOS database, which showed a significant improvement in organ procurement and an
increased odd of a brain dead patient becoming an
organ donor if treated with a triple hormonal
therapy consisting of methylprednisolone, T3/T4,
and vasopressin (73). Various other studies have
demonstrated beneficial effects of hormonal therapy on the hemodynamically unstable organ donor
with subsequent improvement of graft function
(25, 74, 75), altogether leading to the implementation of hormonal resuscitation of hemodynamically unstable potential organ donors (left ventricular
ejection fraction < 45%) with a combination of
T3 (4 lg bolus, infusion at 3 lg/h), vasopressin
(1 U bolus, infusion at 0.5–4 U/h; SVR 800–1200),
methylprednisolone (15 mg/kg bolus), and insulin
(> 1 U/h; blood glucose levels 120–180 mg/dL) in
the UNOS standardized donor management protocol (18). Severe brain injury results in a stressassociated rise in serum cortisol and may therefore
produce relative adrenal insufficiency (35). Together with a decrease in serum cortisol levels after
loss of anterior pituitary gland function and the
inflammatory processes associated with brain
Critical care management of potential organ donors
death (29, 76–78), treatment with corticosteroids
has been proven to be beneficial in potential organ
donors both because of their immunomodulatory
effects and their stabilization of systemic vascular
resistance with catecholamine-sparing effects (34).
The optimal dose, however, remains uncertain.
Hyperglycemia is another common event after
brain death and arises from massive catecholamine
release, infusion of dextrose-containing fluids, and
peripheral insulin resistance. Because hyperglycemic damage to pancreatic beta cells is linked with
graft dysfunction in pancreatic transplants (16, 79),
strict control of blood glucose levels by means of
an insulin infusion is essential to achieve euglycemia (80–150 mg/dL) (23).
Supportive critical care
Hypothermia
Loss of hypothalamic thermoregulation following
cerebral herniation, peripheral vasodilatation because of the deactivation of sympathetic tone
resulting in increased heat emission and reduction
in metabolic activity lead to the inability of keeping
body temperature within the physiological range
(poikilothermia) and, most frequently, to hypothermia (80). Because hypothermia may cause
adverse events such as cardiac dysfunction, arrhythmias, deterioration of microcirculation and
oxygen consumption, coagulopathy, or cold-induced diuresis, core body temperature should be
maintained at ‡ 35C, e.g., by means of convective
warming blankets or warming of fluids.
because of central diabetes insipidus, excessive
fluid replacement to ensure hemodynamic stability
or the aftermath of osmotic diuresis with mannitol
for the treatment of increased intracranial pressure.
Because elevated sodium levels have been associated with higher rates of primary graft failure (36,
69), it is essential to compensate hypernatremia by
infusing 5% dextrose solution in water or half
normal saline (0.45%) as well as treating potential
causes, e.g., hormonal replacement with arginine–
vasopressin or desmopressin. Besides, maintenance
of metabolic and respiratory acid–base balance has
to be considered in potential organ donors. Respiratory alkalosis following hyperventilation during
the treatment of increased intracranial pressure
worsens tissue oxygenation so that normocapnia
should be achieved. On the other hand, metabolic
acidosis most likely resulting from an increase in
metabolic activity because of a lack of T3 in
potential organ donors (81) may worsen cardiac
function necessitating correction with trometamol
or sodium bicarbonate (16).
Conclusion
In summary, caring for a brain dead potential
organ donor requires a shift in critical care
therapy from the extensive treatment of increased
intracranial pressure toward strategies to maintain donor organ function. A systematic and
optimized critical care management (as summarized in fig. 2) increases not only the number, but
also the quality of suitable organs, aiming at an
optimal outcome for the recipients.
Coagulopathy
Conflicts of interest
Because of the pathophysiological changes described previously, brain death is associated with
an increased risk of disseminated intravasal coagulopathy one has to be aware of (15). Generally,
accepted goals of therapy include an international
normalized ratio (INR) of < 1.5 and a platelet
count of > 50 000/mm3, and replacement of
clotting factors with fresh frozen plasma and
platelet transfusions should be adjusted to these
goals; however, to date there are no conclusive
evidence-based data available.
CD and RA have no conflicts of interest. BV, ME and AU
have not declared any conflicts of interest.
Maintenance of electrolyte levels as well as metabolic
and respiratory acid–base balance
Disturbances in electrolyte levels, mainly hypernatremia (serum sodium level > 150 mM) and
hypokalemia, occur frequently in brain dead
potential organ donors and are a result of polyuria
References
1. Lopez-Navidad A, Domingo P, Caballero F. Organ
shortage: viability of potential organ donors and possible
loss depend on health care workers who are responsible for
the organ procurement program. Transplant Proc 1997:
29: 3614.
2. Grossman R. Early enteral formula administration. Crit
Care Med 1995: 23: 436.
3. Nygaard CE, Townsend RN, Diamond DL. Organ
donor management and organ outcome: a 6-year from a
level 1 trauma center. J Trauma 1990: 30: 728.
4. Van Bakal AB. The cardiac transplant donor: identification, assessment, and management. Am J Med Sci 1997:
314: 153.
5. Novitzky D. Detrimental effects of brain death on the
potential organ donor. Transplant Proc 1997: 29: 3770.
6. Novitzky D. Donor management: state of the art.
Transplant Proc 1997: 29: 3773.
7
Dictus et al.
7. Tuttle-Newhall JE, Collins BH, Kuo PC, Schoeder
R. Organ donation and treatment of the multi-organ donor. Curr Probl Surg 2003: 40: 266.
8. Shivarlkar B, Van Loon J, Wieland W et al. Variable
effects of explosive or gradual increase of intracranial
pressure on myocardial structure and function. Circulation
1993: 87: 230.
9. Carber C, Manyalich M, Valero R, Garcia-Fages
LC. Timing used in the different phases of the organ
procurement process. Transplant Proc 1992: 24: 22.
10. Kosieradzki M, Kuczynska J, Piwowarska J et al.
Prognostic significance injury occurring in the kidney donor. Transplantation 2003: 75: 1221.
11. Lagiewska B, Pacholczyk M, Szostek M, Walaszewski J, Rowinski W. Hemodynamic and metabolic disturbances observed in brain-dead organ donors. Transplant
Proc 1996: 28: 165.
12. Finfer S, Bohn D, Colpitts D, Cox P, Fleming F,
Barker G. Intensive care management of pediatric organ
donors and its effect on post transplant organ function.
Intensive Care Med 1996: 22: 1424.
13. Van der Hoeven JA, Ter Horst GJ, Molema G et al.
Effects of brain death and hemodynamic status on function and immunologic activation of the potential donor
liver in the rat. Ann Surg 2000: 232: 804.
14. Kusaka M, Pratschke J, Wilhelm MJ et al. Activation
of inflammatory mediators in rat renal isografts by donor
brain death. Transplantation 2000: 69: 405.
15. Hefty TR, Cotterell LW, Fraser SC, Goodnight SH,
Hatch TR. Disseminated intravascular coagulation in
cadaveric organ donors. Incidence and effect on renal
transplantation. Transplantation 1993: 55: 442.
16. Hoemme R, Neeser G. Organ donation. Anaesthesist
2007: 56: 1291.
17. Power BM, Van Heerden PV. The physiological changes
associated with brain death-current concepts and implantations for treatment of the brain dead organ donor.
Anaesth Intensive Care 1995: 23: 26.
18. Zaroff JG, Rosengard BR, Armstrong WF et al.
Consensus conference report: maximizing use of organs
recovered from the cadaver donor: cardiac recommendations March 28–29 2001, Crystal City, Va. Circulation
2002: 106: 836.
19. Deman A, Peeters P, Sennesael J. Hydroxyethyl starch
does not impair immediate renal function in kidney
transplant recipients: a retrospective, multicenter analysis.
Nephrol Dial Transplant 1999: 14: 1517.
20. Reilly PM, Grossman M, Rosengard BRE. Lung
procurement from solid organ donors: role of fluid
resuscitation in procurement failures. Chest 1996: 110:
222S.
21. Rosengard BR, Feng S, Alfrey EJ 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.
22. Hevesi ZG, Lopukhin SY, Angelini G, Coursin DB.
Supportive care after brain death for the donor candidate.
Int Anesthesiol Clin 2006: 44: 21.
23. Wood KE, Becker BN, Mccartney JG, DÕAlessandro
AM, Coursin DB. Care of the potential organ donor.
NEJM 2004: 351: 2730.
24. Wheeldom 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.
25. Potter CD, Wheeldon DR, Wallwork J. Functional
assessment and management of heart donors: a rationale
8
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
for characterization and a guide to therapy. J Heart Lung
Transplant 1995: 14: 59.
Debaveye YA, Van den Berghe GH. Is there still a place
for dopamine in the modern intensive care unit? Anesth
Analg 2004: 98: 461.
Marik PE, Mohedin M. The contrasting effects of
dopamine and norepinephrine on systemic and splanchnic
oxygen utilization in hyperdynamic sepsis. JAMA 1994:
272: 1354.
Tilney NL, Paz D, Ames J, Gasser M, Laskowski I,
Hancock WW. Ischemia-reperfusion injury. Transplant
Proc 2001: 33: 843.
Amado JA, Lopez-Espadas F, Vazquez-Barquero A
et al. Blood levels of cytokines in brain-dead patients:
relationship with circulating hormones and acute-phase
reactants. Metabolism 1995: 44: 812.
Stangl M, Zerkaulen T, Theodorakis J et al. Influence
of brain death on cytokine release in organ donors and
renal transplants. Transplant Proc 2001: 33: 1284.
Iwai A, Sakano T, Uenishi M, Sugimoto H, Yoshioko
T, Sugimoto T. Effects of vasopressin and cathecholamines on the maintenance of circulatory stability in braindead patients. Transplantation 1989: 48: 613.
Katz K, Lawler J, Wax J, OÕConnor R, Nadkarni V.
Vasopressin pressor effects in critically ill children during
evaluation for brain death and organ recovery. Resuscitation 2000: 47: 33.
Hunt SA, Baldwin J, Baumgartner W et al. Cardiovascular management of a potential heart donor: a statement from the transplantation committee of the American
College of Cardiology. Crit Care Med 1996: 24: 1599.
Marik PE, Varon J, Trask T. Management of head
trauma. Chest 2002: 122: 699.
Howlett TA, Keogh AM, Perry L, Touzel R, Rees
LH. Anterior and posterior pituitary function in brain
stem dead donors. A possible role for hormonal replacement therapy. Transplantation 1989: 47: 828.
Gramm HJ, Meinhold H, Bickel U et al. Acute endocrine failure after brain death? Transplantation 1992: 54:
851.
Shah VR. Aggressive management of multiorgan donor.
Transplant Proc 2008: 40: 1087.
Avlonitis VS, Fisher AJ, Kirby JA, Dark JH. Pulmonary transplantation: the role of brain death in donor lung
injury. Transplantation 2003: 75: 1928.
Kutsogiannis DJ, Pagliarello G, Doig C, Ross H,
Shemie SD. Medical management to optimize donor organ potential: review of the literature. Can J Anaesth 2006:
53: 820.
Wood KE, Coursin DB. Intensivists and organ donor
management. Curr Opin Anaesthesiol 2007: 20: 97.
Pennefather SH, Bullock RE, Dark JH. The effect of
fluid therapy on alveolar arterial oxygen gradient in brain
dead organ donors. Transplantation 1993: 56: 1418.
Aziz TM, El-Gamel A, Saad RA, Migliore M, Campbell
CS, Yonan NA. Pulmonary vein gas analysis for assessing
donor lung function. Ann Thorac Surg 2002: 73: 1599.
Gabbay E, Williams TJ, Griffiths AP et al. Maximizing
the utilization of donor organ offered for lung transplantation. Am J Respir Crit Care Med 1999: 160: 265.
Follette D, Rudich S, Bonacci C, Allen R, Hoso A,
Albertson T. Importance of an aggressive multidisciplinary management approach to optimize lung donor
procurement. Transplantation Proc 1999: 31: 169.
Tanaka N. Radiologic-pathologic correlation of experimental bleomycin-induced pneumonitis. Nippon Iqaku
Hoshasen Gakkai Zasshi 1993: 53: 1392.
Critical care management of potential organ donors
46. Wilheim S, Maze M. Controversial issues in adult and
paediatric ambulatory anaesthesia: is there a role for
alpha-2 agonist in conscious sedation in adults and
paediatric ambulatory surgical practice. Curr Opin Anaesthesiol 2000: 13: 619.
47. Postema S, Pattynama PM, van Rijswijk CS, Trimbos
JB. Cervical carcinoma: can dynamic contrast enhanced
MR imaging help predict tumor aggressiveness. Radiology
1999: 210: 217.
48. De Boer ML, Hu J, Kalvakolanu DV, Hasdav JD,
Cross AS. INF gamma inhibits lipopolysaccharide-induced interleukin 1 beta in primary murine macrophages
via a Stat 1 dependent pathway. J Interferon Cytokine Res
2001: 21: 485.
49. Van der Wounde FJ, Ferrario F. Renal involvement in
ANCA associated systemic vasculitis. J Nephrol 1999: 12:
105.
50. Itoh M, Kuroda K. Impressions on 11th international
conference on Nagative Strand Viruses. Uirusu 2000: 50:
319.
51. Zivna H, Zivny P, Navratil P et al. The role of cytokines
and antioxidant status in graft quality prediction. Transplant Proc 1999: 31: 2094.
52. Nagareda T, Kinoshita Y, Tanaka A et al. Clinicopathology of kidneys from brain dead patients treated with
vasopressin and epinephrine. Kidney Int 1993: 43: 1363.
53. Pratschke J, Wilhelm MJ, Kusaka M et al. Accelerated
rejection of renal allograft from brain dead donors. Ann
Surg 2000: 232: 263.
54. Schnuelle P, Berger S, de Boer J, Persijn G, van der
Wounde FJ. Effects of catecholamine application to brain
dead donors on graft survival in solid organ transplantation. Transplantation 2001: 72: 455.
55. Schnuelle P, Lorenzo D, Mueller A, Trede M, Van
der wounde FJ. Donor catecholamine use reduces acute
allograft rejection and improves graft survival after
cadaveric renal transplantation. Kidney Int 1999: 56: 738.
56. Singer AC, Wong CS, Crowley DE. Differential enantioselective transformation of atropisomeric polychlorinated biphenyls by multiple bacterial strains with different
including compounds. Appl Environ Microbiol 2002: 68:
5756.
57. Tepel M, van der Giet M, Schwarzfeld C, Laufer U,
Liermann D, Zidek W. Prevention of radiographic contrast agent induced reductions in renal function by acetylcysteine. N Engl J Med 2000: 343: 180.
58. Efrati S, Dishy V, Averbukh M et al. The effect of Nacetylcycteine on renal function, nitric oxide and oxidative
stress after angiography. Kidney Int 2003: 64: 2182.
59. Briguori C, Manganelli F, Scarpato P et al. Acetylcysteine and contrast agent associated nephrotoxicity. J
Am Coll Cardiol 2002: 40: 298.
60. Diaz-Sandoval LJ, Kosowsky BD, Losordo DW. Acetylcysteine to prevent angiography related renal tissue injury (the APART trial). Am J Cardiol 2002: 89: 356.
61. Kay J, Chow WH, Chan TM et al. Acetylcysteine for
prevention of acute deterioration of renal function following elective coronary angiography and intervention: a
randomized controlled trial. JAMA 2003: 289: 553.
62. Merten GJ, Burgess WP, Rittase RA, Kennedy TP.
Prevention of contrast induced nephropathy with sodium
bicarbonate: an evidence based protocol. Crit Pathw
Cardiol 2004: 3: 138.
63. Ploeg RJ, DÕAlessandro AM, Knechtle SJ et al. Risk
factoers for primary dysfunction after liver transplantation – a multivariate analysis. Transplantation 1993: 55:
807.
64. Clavien PA, Harvey PR, Strasberg SM. Preservation
and reperfusion injuries in liver allografts. An overview
and synthesis of current studies. Transplantation 1992: 53:
957.
65. Brokelman W, Stel AL, Ploeg RJ. Risk factors for
primary dysfunction after liver transplantation in the
university of Wisconsin solution era. Transplant Proc
1999: 31: 2087.
66. Porte RJ, Ploeg RJ, Hansen B et al. Lonh term graft
survival after liver transplantation in the UW era: late effects of cold ischemia and primary dysfunction. European
Multicenter Study Group. Transpl Int 1998: 11(Suppl. 1):
S164.
67. Figueras J, Busquets J, Grande L et al. The deleterious
effect of donor high plasma sodium and extrended preservation in liver transplantation. A multivariate analysis.
Transplantation 1996: 61: 410.
68. Gonzalez FX, Rimola A, Grande L et al. Predictive
factors of early postoperative graft function in human liver
transplantation. Hepatology 1994: 20: 565.
69. Totsuka E, Dodson F, Urakami A et al. Influence of
high donor serum sodium levels on early postoperative
graft function in human liver transplantation: effect of
correction of donor hypernatremia. Kidney Transpl Surg
1999: 5: 421.
70. Sazontseva IE, Kozlov IA, Moisuc YG, Ermolenko
AE, Afonin VV, Ilnitskiy VV. Hormonal response to
brain death. Transplant Proc 1991: 23: 2467.
71. Holmes CL, Patel BM, Russell JA, Walley KR.
Physiology of vasopressin relevant to management of
septic shock. Chest 2001: 120: 989.
72. Novitzky D, Cooper DK, Reichart B. Hemodynamic
and metabolic responses to hormonal therapy in brain
dead potential organ donors. Transplantation 1987: 43:
852.
73. Rosendale JD, Kauffman HM, McBride MA et al.
Aggressive pharmacologic donor management results in
more transplanted organs. Transplantation 2003: 75:
482.
74. Jeevanandam V. Triiodothyronine: spectrum of use in
heart transplantation. THYROID 1997: 7: 139.
75. Salim A, Vassiliu P, Velmahos GC et al. The role of
thyroid hormone administration in potential organ donors. Arch Surg 2001: 136: 1377.
76. Pratschke J, Wilhelm MJ, Kusaka M et al. Brain death
and its influence on donor organ quality and outcome after
transplantation. Transplantation 1999: 67: 343.
77. Birks EJ, Burton PB, Owen V et al. Elevated tumor
necrosis factor alpha and interleukin 6 in myocardium and
serum of malfunctioning donor hearts. Circulation 2000:
102(Suppl. 3): III 52.
78. Nijboer WN, Schuurs TA, van der Hoeven JA et al.
Effects of brain death on stress and inflammatory response
in the human donor kidney. Transplant Proc. 2005 Jan–
Feb: 37: 367–9.
79. 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.
80. Smith M. Physiologic changes during brain stem death
lessons for management of the organ donor. J Heart Lung
Transplant 2004: 23: S217.
81. Powner DJ, Hendrich A, Lagler RG, Ng RH, Madden RL. Hormonal changes in brain dead patients. Crit
Care Med 1990: 18: 702.
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