Impact of Delirium on Distre
of Life, and Cognition 6 M
Hematopoietic C
James R. Basinski,1 Catherine M
Karen L. Syrjala,1,3 J
Delirium commonly occurs during myeloablative hemato
about how delirium during the acute phase of HCT affe
(HRQOL), and neurocognitive functioning. This prospe
atien
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ared
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From the
versit
Ohio
Biobe
Cente
C.M. Alfa
of Ca
Institu
Financial d
Correspon
of Psy
ton S
Seattle, WA 98125 (e-mail: fann@u.washington.edu).Received May 15, 2009; accepted January 6, 2010
 2010 El
1083-8791
doi:10.101
824health-related quality of life (HRQOL) in p
with either cancer or those who received HCT
A prospective, longitudinal study of patie
dergoing HCT indicates that physical, psycho
and vocational recovery begins during the fi
posttransplantation and continues over at le
next 3 to 5 years [11]. The same research gro
found that patients in the first post-HCT year h
sistent declines in grip strength and motor de
State University, Columbus, Ohio; and 3Department of
havioral Sciences, Fred Hutchinson Cancer Research
r, Seattle, Washington.
no is now with the Office of Cancer Survivorship, Division
ncer Control and Population Sciences, National Cancer
te, Bethesda, MD.
isclosure: See Acknowledgments on page 830.
dence and reprint requests: Jesse Fann, MD, Department
chiatry and Behavioral Sciences, University of Washing-
chool of Medicine, Box 356460, 1959 NE Pacific Street,on longer term outcomes of cognition, distress, andton;
2College of Public Health, Comprehensive Cancer
Center, and Institute for Behavioral Medicine Research, TheDUCTION
rium is a common neuropsychiatric complica-
ematopoietic cell transplantation (HCT), re-
n up to 50% of patients in the first 4 weeks
splantation [1,2]. The high rates of delirium
ts undergoing HCT appear linked to having
acute systemic disease and being exposed to
t interventions with deliriogenic or cognitive
Potential treatments that may precipitate
delirium include: psychoactive medications
opioid analgesics, sedatives, corticosteroid
anticholinergics [3], as well as total body irra
(TBI) [4] and resultant infections [5].
By definition, delirium is characterized by a
ible disturbance of consciousness and change in
tion or perception [6]. It is independently ass
with significant morbidity, mortality, and fun
decline across multiple populations [7]. Deleter
fects onmortality [8,9], length of hospital stay [1
performance status [8] have been noted in hosp
cancer patients who develop delirium. To our
edge, no studies have examined the effects of d
1Department of Psychiatry and Behavioral Sciences, Uni-
y of Washington School of Medicine, Seattle, Washing-Biol Blood Marrow Transplant 16: 824-831 (2010)  2010 Elsevier Inc. All rights reserved.
KEY WORDS: Delirum, Stem cell transplantation, Distress, Quality of life, Cognition, Outcomesmonths and 1 year in 90 patients undergoing HCT. P
and subjective neuropsychological functioning befor
year. Patients with a delirium episodewithin the 4 we
at 6 months (P\.004) and at 1 year (P\.03), comp
with delirium also had worse symptoms of depressi
lirium had worse physical health on the SF-12 at 6 mo
year (P\.03). At both 6 months and 1 year, patients
.009) and executive functioning (P\.006). Delirium
with persistent distress, decreased HRQOL, and sub
1 year.sevier Inc. All rights reserved.
/$36.00
6/j.bbmt.2010.01.003ss, Health-Related Quality
onths and 1 Year after
ell Transplant
. Alfano,2 Wayne J. Katon,1
esse R. Fann1,3
poietic cell transplantation (HCT). Little is known
cts long-term distress, health-related quality of life
ctive, cohort study examines these outcomes at 6
ts completed a battery assessing distress, HRQOL,
eiving their first HCTas well as at 6 months and 1
fter HCT had significantly more distress and fatigue
with patients without delirium. At 1 year, patients
d post traumatic stress (P\.03). Patients with de-
(P\.03) and worse mental health on the SF-12 at 1
delirium after HCTreported worse memory (P\
g the acute phase of HCT is significantly associated
ve neurocognitive dysfunction at both 6 months andcognition [12]. In contrast, a prospective study of neu-
rocognitive changes in the first 20 months in patients
with hematologic malignancies being treated with

HCT at the FredHutchinson Cancer Research Center
(FHCRC).
ing insight, disinhibition, and impaired attention
Biol Blood Marrow Transplant 16:824-831, 2010 825Impact of Delirium 6 Months and 1 Year after HCTProcedures
Study procedures for this cohort have been previ-
ously reported [2]. The FHCRC institutional review
board approved the protocol and all study procedures.
All study patients received and signed written in-
formed consent. Patients completed a comprehensive
battery before transplantation measuring distress,
HRQOL, and neuropsychological functioning. The
results of the readministration of a subset of this bat-
tery at 30 days and the full battery again at 80 has
been previously reported [14]. At 6 months and 1
year, patients again completed a subset of this battery.
From 7 days pretransplantation until 30 days post-
transplantation, study investigators or trained research
nurses screened patients 3 times per week with a brief
delirium assessment battery, targeted to the same time
each day (Monday, Wednesday, and Friday).
Independent Variables
We measured delirium using the Delirium Rating
scale (DRS), a 10-item, clinician-rated scale (score
range: 0-32) that rates delirium severity over 24 hoursHCT compared to a reference group of patients re-
ceiving nonmyeloablative therapies found persistent
declines in attention and executive function in addition
to psychomotor function in both groups [13]. It re-
mains unclear whether delirium contributes to the
risk of persistent functional and cognitive decrements
in HCT patients.
The goal of this study was to investigate the asso-
ciation of delirium during acute phase treatment with
distress, HRQOL, and cognition 6 months and 1
year after HCT. Fifty percent of this previously de-
scribed cohort had a delirium episode during the first
4 weeks after HCT [2]. Previous outcome results
from this cohort have demonstrated delirium’s adverse
impact on depression, anxiety, and fatigue at 30 days as
well as worse anxiety, fatigue, distress, HRQOL, exec-
utive functioning, attention, and processing speed at
80 days [14]. In the current analysis, we hypothesized
that patients who had experienced a delirium episode
in the acute phase of HCTwould have worse cognitive
functioning, distress, and HRQOL at the extended
follow-up points of 6 months and 1 year compared to
patients who had not experienced delirium.
PATIENTS AND METHODS
Patients
Ninety patients between the ages of 22 to 62 years
were recruited before their first myeloablative allo-
genic or autologous bone marrow or peripheral blood(score range: 0-10; higher scores5more severe behav-
ioral disturbance) [21].
The Modified Memory Questionnaire (MMQ) is
a 35-item measure of subjective memory function
(score range: 0-4; higher scores 5 greater memory
dysfunction) [22].using sources including patient interview, mental sta-
tus examination, medical history and tests, and collat-
eral observation from nursing staff and family [15].We
defined a delirium episode as a DRS score .12 on at
least 2 of 3 consecutive assessments.
Dependent Variables
Distress
The Symptom Checklist-90-R (SCL-90) is a stan-
dardized self-report inventory of psychologic symp-
toms (score range: 0-4; higher scores 5 greater
distress), which has been used with cancer patients
[16,17]. It has been shown to have high reliability
and validity in medical patients. We report on the
depression and anxiety subscales.
The Profile of Mood States (POMS) Fatigue sub-
scale is the 7-item subset of a valid and reliable scale of
mood disturbance (score range: 0-4; higher scores 5
greater fatigue) widely used in cancer patients [18].
The Cancer and Treatment Distress scale is the
mean of a 29-item self-report questionnaire (score
range: 0-3; higher scores 5 greater distress), devel-
oped in the HCT population, that measures cancer
specific distress distinct from general anxiety or
depression [11].
The Post Traumatic Stress scale was developed by
the fourth author (K.L.S.) for use in HCT patients. It
is similar to the Patient Health Questionnaire (PHQ)
[19] as a self-report of symptoms for diagnosing
PTSD corresponding to Diagnostic and Statistical Man-
ual IV psychiatric criteria [6]. The measure includes 11
symptom items scored for frequency from 0 5 not at
all to 65 several times a day, and 1 item on overall im-
pact rated from 05 these things have not happened to
me to 5 5 severely disturbing, they really have an
impact on how I feel and what I do.
HRQOL
The 12 item version of the Short-Form Health
Survey (SF-12) measures physical and mental
HRQOL using 2 standardized summary measures of
physical and mental health (higher scores 5 better
functioning) [20].
Neuropsychological functioning
TheNeurobehavioral Rating scale (NBRS) is a 27-
item structured self-report questionnaire of executive
functioning measuring behavioral disturbance includ-