Impact of Delirium on Decision-Making Capacity After
Hematopoietic Stem-Cell Transplantation
Thomas Zaubler, M.D., M.P.H., Jesse R. Fann, M.D., M.P.H.
Sari Roth-Roemer, Ph.D., Wayne J. Katon, M.D.
Rami Bustami, Ph.D., Karen L. Syrjala, Ph.D.
Background: Delirium is a common complication of myeloablative hematopoietic stem-cell
transplantation (HSCT), yet no studies have explored the later effects of an episode of delirium
in this setting on patients’ decision-making capacity after the acute symptoms of delirium have
resolved. Objective: The authors assessed the impact of delirium during the acute phase of my-
eloablative HSCT on later decision-making capacity. Method: Decision-making capacity was
assessed with the MacArthur Competence Assessment Tool in 19 patients before they received
their first HSCT and at 30 and 80 days post-transplantation. Delirium was assessed 3 times per
week with the Delirium Rating Scale and the Memorial Delirium Assessment Scale from 7 days
pre-transplantation through 30 days post-transplantation. Results: Although there was little vari-
ance in the pre-treatment scores, with most patients showing very high or perfect scores on deci-
sion-making abilities, a multivariate regression model showed that delirium was predictive of a
lower reasoning score at Day 30 post-transplantation. Conclusion: Patients who experienced a
delirium episode during the acute phase of HSCT were not likely to develop clinically meaning-
ful impairments in decision-making capacity post-transplantation, although they evidenced minor
impairment in their reasoning ability. (Psychosomatics 2010; 51:320–329)
Although the doctrine of informed consent has beenemphasized as an integral and essential component of
the relationship between physician and patient, there has been
very little research investigating how the process of obtaining
informed consent can be operationalized in the clinical set-
ting. In order for a patient to provide informed consent,
several critical requirements must be met: the patient must be
able to make a voluntary decision without coercion or undue
influence; a disclosure of information about the patient’s
medical illness and risks and benefits of treatment options
must be made; the patient must have the capacity to make a
decision that reflects a clear understanding and appreciation
of the nature of his or her medical illness and treatment
options and must have an ability to think reasonably about the
risks and benefits of various treatment options.1 There has
been a growing but still small body of research providing
empirical evidence of clinical factors that may impair deci-
sion-making capacity.
Although some preliminary investigations have found
that certain medical illnesses may lead to impaired deci-
sion-making capacity,2 there has been almost no empirical
exploration of risk factors for impaired decision-making
capacity in the cancer setting. To our knowledge, there
Received October 15, 2008; revised December 18, 2008; accepted De-
cember 19, 2008. From the Dept. of Psychiatry and Behavioral Health,
Morristown Memorial Hospital, Atlantic Health, Morristown, NJ; the
Dept. of Biobehavioral Sciences, Fred Hutchinson Cancer Research Cen-
ter, Seattle, WA; the Dept. of Psychiatry and Behavioral Sciences, Uni-
versity of Washington, Seattle, WA; Arizona Medical Psychology,
Scottsdale, AZ; and the Office of Grants and Research, Atlantic Health,
Morristown, NJ. Send correspondence and reprint requests to Thomas
Zaubler, M.D., M.P.H., Morristown Memorial Hospital, 100 Madison
Ave., Morristown, NJ 07962. e-mail: thomas.zaubler@atlantichealth.org
© 2010 The Academy of Psychosomatic Medicine
320 http://psy.psychiatryonline.org Psychosomatics 51:4, July-August 2010

have been no studies investigating this among some of the
most acutely ill cancer patients, who are undergoing he-
matopoietic stem cell transplantation (HSCT). Although
myeloablative HSCT can be a life-saving treatment that
may be the sole option for long-term survival for many
patients with cancer, it entails a neurotoxic conditioning
regimen that often leads to multiple short-term and long-
term complications, including cognitive impairment.3–6
Providing informed consent among patients undergoing
HSCT is an arduous and challenging process, both because of
the extensive amount of information that needs to be con-
veyed to the patient and because the toxicity of the treatment
may lead to slowed information-processing6 and potentially,
impaired decision-making capacity. Myeloablative HSCT
entails a conditioning treatment with high-dose chemother-
apy, often with total body irradiation, followed by hemato-
poietic stem-cell transplantation. Patients may experience di-
rect effects of the chemotherapeutic agents as well as
subsequent immunologically-mediated complications from
the stem-cell transplantation, such as graft-versus-host dis-
ease or the medications used to treat graft-versus-host dis-
ease.7–9 Delirium is a common neuropsychiatric complica-
tion occurring in patients undergoing HSCT.
Delirium occurs in 25% to 40% of patients with can-
cer,10–12 45% to 85% of those with advanced cancer,13–16
and up to 50% of patients during the 4 weeks after my-
eloablative HSCT.17 Delirium is often accompanied by
increased distress, fatigue, and pain.17,18 Delirium in pa-
tients with cancer, in general, has been associated with
adverse outcomes, including decreased performance sta-
tus;19 increased pain and use of breakthrough analge-
sia;20,21 longer length of hospital stay;22,23 increased dis-
tress for the patient and his/her spouse, caregivers, and
nurses;24,25 and decreased survival.16,19 Patients who ex-
perience delirium after myeloablative HSCT have been
found to have worse distress 30 days later and impaired
neurocognitive abilities, persistent distress, and decreased
quality of life at 80 days than those without delirium.26
Similar affective and neuropsychological deficits as those
found subsequent to a delirium episode have, in both med-
ical and psychiatric settings, been shown to be associated
with impaired decision-making capacity.27–29 The evi-
dence, therefore, suggests that although the overt symp-
toms of delirium may be short-lived, there may be a lasting
impact of delirium on affective functioning and cognition,
thereby affecting decision-making capacity. Although it
has been well established that the neurocognitive deficits
associated with an acute episode of delirium are likely to
lead to impairments in decision-making capacity,30–32 no
studies have investigated the “downstream” effect on de-
cision-making capacity of an index episode of delirium
once the acute symptoms have resolved.
This prospective study investigated the impact of de-
lirium during the acute phase of myeloablative HSCT on
30- and 80-day decision-making capacity. Although the
manifest symptoms associated with an index episode of
delirium will most likely resolve by 30 and 80 days post-
transplantation, subclinical problems with cognition and
affective functioning may persist for many weeks, leading
to impaired decision-making capacity. Consistent with re-
search in general-hospital samples, we hypothesized that
patients who experienced a delirium episode after HSCT
would demonstrate some degree of impairment in deci-
sion-making capacity at 30 and 80 days, as compared with
patients who did not experience a delirium episode.
METHOD
Subjects
Nineteen patients, ages 25–58 years, treated at the
Fred Hutchinson Cancer Research Center, were recruited
before their first myeloablative allogenic or autologous
marrow or peripheral blood HSCT. A broad range of can-
cer diagnoses was represented (Table 1).
Procedures
Study procedures from this cohort are detailed in a
previous publication.17 All procedures were approved by
the Institutional Review Board, and study patients signed
written informed consent statements to participate before
beginning transplantation conditioning. Before condition-
ing, patients completed a comprehensive battery assessing
health-related quality of life (HRQoL), distress, and neu-
ropsychological functioning. They also completed the
MacArthur Competence Assessment Tool for Treatment
(MacCAT–T), an assessment designed to evaluate deci-
sion-making capacity. A subset of assessments, including
the MacCAT–T, was given at 30 days post-transplanta-
tion, and the full battery was repeated at 80 days post-
transplantation. At 7 days pre-transplantation, during con-
ditioning, and through Day 30 post-transplantation, trained
research nurses or investigators assessed patients with a
brief delirium- (diagnosis, severity), distress-, and pain-
assessment battery 3 times per week targeted to the same
time each day (Monday, Wednesday, and Friday).17 Pa-
tients with delirium were able to provide outcome data,
except in the most severe cases.
Zaubler et al.
321Psychosomatics 51:4, July-August 2010 http://psy.psychiatryonline.org