ber of organs successfully procured from each available
donor. With the ongoing organ shortage, a more aggres-
sive pharmacologic approach in caring for brain-dead
donors may be necessary to increase both the number
and quality of viable organs eligible for transplantation.
The United Network for Organ Sharing (UNOS) has
created a Critical Pathway for the Organ Donor as a
guide to optimal care of brain-dead donors until the
point of organ recovery.1 In addition to fluid and elec-
trolyte replacement, as well as vasopressor and inotropic
support, the UNOS donor management protocol recom-
mends the use of hormonal resuscitation as a means of
maintaining donor metabolic stability. This review will
Solid-organ transplantation is considered the treat-ment of choice in patients with end-stage hepatic,
renal, cardiac, and pulmonary disease. The success of
transplantation in offering patients with end-stage
organ disease a chance to live longer and fuller lives
has also inevitably increased the need for an expanded
pool of organ donors. Today, more than 80000 people
in the United States are on the waiting list for organ
transplantation, which is an increase of more than 200%
over the past 10 years.1 Meanwhile, the total number of
cadaveric organ donors has increased by only 35%
from 1992 to 2001. Although there is approximately a
7% increase in all organ donors per year, this increase
is largely due to the rising number of living donors
(Figure). No more than 15000 deceased brain-dead
donors are estimated to be available each year.1
Increasing the donor pool to meet the rising need
for transplantation will require higher donor consent
rates, as well as a continued effort to increase the num-
Critical care pharmacy in donor management
Significant systemic changes occur following neurologic insult and subsequent
brain death. If left untreated, the hemodynamic instability and neuroendocrine
alterations that ensue may significantly affect the quality of the donor organs, and
contribute to posttransplant allograft dysfunction. A number of pharmacologic
interventions are often implemented in an attempt to stabilize donor hemodynam-
ics and optimize organ perfusion, thereby increasing the number and quality of
cadaveric donor organs available for transplantation. This review provides a sum-
mary of these interventions, with an emphasis placed on hormonal resuscitation,
which involves utilizing such agents as thyroxin, vasopressin, insulin, and corti-
costeroids. (Progress in Transplantation. 2004;14:105-113)
Paula V. Phongsamran,
PharmD
University of Southern California, Los
Angeles, Calif
To purchase reprints, contact:
The InnoVision Group
101 Columbia, Aliso Viejo, CA 92656
Phone (800) 809-2273 (ext 532) or
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Fax (949) 362-2049
E-mail reprints@aacn.org
105Progress in Transplantation, Vol 14, No. 2, June 2004
Used with permission from the United Network for Organ Sharing.
7000
6000
5000
4000
3000
2000
1000
0
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
Deceased and living donors, 1992-20011
s s
s s
s s s
s s s
n n
n
n
n n
n
n
n
n
s Deceased n Living
Notice to CE enrollees:
A closed-book, multiple-choice examination following
this article tests your ability to accomplish the follow-
ing objectives:
1. Explain the rationale for maximizing organ
procurements from donors
2. Describe the effect desired with hormonal
resuscitation of the donor
3. Identify the optimal drugs and doses for donor
management
Phongsamran6_04.qxd 5/11/04 11:49 AM Page 105

focus primarily on the agents used in hormonal resusci-
tation; that is, vasopressin, triiodothyronine (T3) and L-
thyroxine (T4), corticosteroids, and insulin.
Physiological Changes
Associated With Brain Death
Profound systemic changes may occur following
neurologic insult and subsequent brain death. These
changes involve a somewhat predictable cascade of
events leading to significant hemodynamic and neuro-
endocrine alterations in the donor. These complica-
tions may occur in 80% to 85% of donors and could
adversely affect the quality of the donor organ(s) and
the success of the procurement.2 These changes may
also contribute to development of primary graft dys-
function after transplantation.
The first phase after massive central injury is the
onset of a sympathetic, or autonomic, “storm,”
whereby significant amounts of norepinephrine and
epinephrine are released into the circulation.2,3 A
hyperdynamic state characterized by systemic arterial
hypertension, tachycardia, increased cardiac output,
and cardiac arrhythmias ensue.3 An eventual depletion
of catecholamines and a transition into a normotensive
or hypotensive phase follow as a result of widespread
systemic vasodilation.4 The inotropic and chronotropic
function of the heart becomes impaired, and cardiac
output inevitably falls, with subsequent underperfu-
sion of vital organs.
Brain death may also produce a variety of neuro-
endocrine changes as a result of hypothalamic dys-
function. In these situations, temperature regulation is
lost and hormonal secretion is impaired; this is mani-
fested clinically with the onset of hypothermia, dia-
betes insipidus, as well as fluid and electrolyte
disturbances, all of which may further contribute to
donor instability.5-7 Circulating T3 rapidly declines,
with a resultant decrease in mitochondrial function
and intracellular energy production.6 Some studies,
however, suggest that only minimal neuroendocrine
alterations are present in humans after brain death
because of sustained hypothalamic-pituitary perfu-
sion, which may preserve some residual function for a
length of time. The actual amount of endocrine com-
plications that occur and their clinical impact on the
potential organ donor will probably vary with each
individual case and clinical scenario.
Both the early unregulated sympathetic response
and the impaired hypothalamic-pituitary axis may
contribute to the hemodynamic instability seen in
brain-dead donors.4,5 Without intervention, this
inevitably results in detrimental alterations in organ
perfusion and oxygenation. Aggressive donor man-
agement strategies, which include optimizing respira-
tory care, routine implementation of hormone therapy,
and judicious use of volume replacement and hemo-
dynamic support, have been shown to improve recipi-
ent outcomes.5
Fluid Resuscitation,
Vasopressors, and Inotrope Use
Preventing malperfusion to peripheral tissues
requires correcting and maintaining mean arterial
pressure and cardiac output. Initial volume replace-
ment generally entails administration of crystalloid
solutions such as isotonic sodium chloride solution or
Ringer’s lactate solution.8 Albumin or hetastarch may
be added if additional volume expansion is needed.9
Maintenance fluids (eg, 5% dextrose, 5% dextrose in
0.45% saline) can then be administered once adequate
volume expansion is achieved.9 The choice of fluids
will usually be dictated by serum sodium and glucose
levels. In the setting of aggressive fluid management
and potential urinary losses in cases of uncontrolled
diabetes insipidus, serum electrolyte levels must be
checked often. The most common electrolyte distur-
bances encountered are hypernatremia with hypomag-
nesemia, hypocalcemia, hypokalemia, and
hypophosphatemia.5 Monitoring of the metabolic
panel should be performed every 2 hours until severe
deficits are corrected.5
Additional hemodynamic support may be needed
if hypotension persists in severely volume-depleted
organ donors despite aggressive fluid replacement.
Dopamine is generally regarded as the vasopressor of
choice. Dobutamine and isoproterenol are both con-
sidered second-line agents because of their β-adrenergic
mediated peripheral vasodilation and poor tolerabil-
ity.8,9 If adequate blood pressure and urine output are
not achieved with the addition of dopamine with or
without dobutamine, α-receptor–mediated vasocon-
strictors such as epinephrine, norepinephrine, and
phenylephrine should be used.9 As with dopamine, the
goal is to maintain predetermined hemodynamic
parameters using the lowest effective dose. High
doses of α-agonists may exacerbate tissue and organ
hypoperfusion because of excessive peripheral vaso-
constriction, and may lead to worsening of acidosis.
The use of high-dose vasopressors has also been asso-
ciated with reduced graft survival and, therefore,
every effort should be made to wean the donor off of
exogenous catecholamines.
Hormonal Resuscitation
Arginine Vasopressin
Neurogenic diabetes insipidus is a common
observance following brain death due to loss of poste-
rior pituitary function.10 Physiologically, this syn-
drome results from a complete or partial deficit in the
production or release of antidiuretic hormone, and is
clinically manifested as a sudden onset of hypotonic
polyuria, hypernatremia, and elevated serum osmolal-
Phongsamran
106 Progress in Transplantation, Vol 14, No. 2, June 2004
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