COMMENTARIES  Postintensive care syndrome
COMMENTARIES
Postintensive care syndrome
and the role of a follow-up clinic
Joanna L. Stollings and Meghan M. Caylor
Am J Health-Syst Pharm. 2015; 72:1315-23
A
dvancements in the care of criti-
cally ill patients in the intensive
care unit (ICU) setting have
increased patients’ chances of surviv-
ing even the most serious illnesses.
In fact, most studies in this patient
population assign mortality as the
primary outcome measure. However,
as more patients are surviving to ICU
discharge, there is now recognition
of many long-term consequences
of ICU hospitalization that have
formerly gone unidentified. Physical
deficits, such as reduced pulmonary
function after acute respiratory dis-
tress syndrome (ARDS) and muscle
wasting and weakness after pro-
longed ICU stays, can be predicted.1
Researchers are also beginning to
examine the psychological conse-
quences and neurocognitive impair-
ment that may result and continue
for years after ICU discharge.2 This
constellation of impairments and
complications was termed postinten-
sive care syndrome by the Society of
Critical Care Medicine (SCCM) and
defined as “new or worsening prob-
lems in physical, cognitive, or mental
health status arising after a critical ill-
ness and persisting beyond acute care
hospitalization.”3 SCCM also recently
created the Thrive! Task Force with
plans to develop and pilot a patient
support network for this cause.4
This article highlights the long-
term consequences of ICU hospi-
talization and describes potential
evidence-based interventions that
may positively affect patient out-
comes. The concept of the post-ICU
clinic is also presented, including the
vital role that the pharmacist can play
in this novel practice setting.
Long-term consequences of ICU
hospitalization. Impaired pulmo-
nary function. Impaired pulmonary
function in survivors of ARDS is
an area of growing interest, and the
long-term recovery patterns have
been documented. Results of a study
of 109 survivors of ARDS revealed
that 3 months after ICU discharge,
patients demonstrated median total
lung capacity, forced expiratory vol-
ume in one second (FEV1), and six-
minute walk test values of 92%, 75%,
and 49% of their predicted values,
respectively.5 At month 12, median
total lung capacity and FEV1 values
improved to 95% and 86% of their
predicted values, respectively, and
improvement in the six-minute walk
test was also seen. However, the dis-
tance walked remained at 66% of the
predicted value at 12 months after
ICU discharge. Factors contributing
Joanna L. Stollings, Pharm.D., BCPS, is
Medical Intensive Care Unit Clinical Phar-
macy Specialist, Department of Pharmaceuti-
cal Services, Vanderbilt University Medical
Center, Nashville, TN. Meghan M. Caylor,
Pharm.D., BCPS, is Postgraduate Year 2 Criti-
cal Care Resident, University of North Caro-
lina Hospitals, Chapel Hill.
Address correspondence to Dr. Stollings
(joanna.stollings@vanderbilt.edu).
Am J Health-Syst Pharm—Vol 72 Aug 1, 2015
to this limitation included muscle
wasting, weakness, immobility, and
dyspnea.5 Conversely, these patients
did not show additional changes in
pulmonary function tests five years
after ICU discharge.6 The median
six-minute walk test result improved
to just 76% of the predicted value.
The physical component score on
the Medical Outcomes Study 36-item
Short Form Health Survey (SF-36)
remained one standard deviation
below the mean score for age- and
sex-matched controls. Although no
patients returned to their predicted
baseline value at five years, younger
patients did have a significantly
higher rate of recovery than did older
patients (p = 0.002).
During the 2009 influenza A
(H1N1) pandemic, young and previ-
ously healthy individuals developed
H1N1-associated ARDS. One-year
outcomes including lung function
were compared among 12 patients
who received extracorporeal lung
assist (ECLA) and 25 who did not.7
Fifty percent of patients in the ECLA
group versus 40% in the non-ECLA
group showed marked dyspnea at
one year after discharge. Eighty-three
percent of the ECLA group and 64%
of the non-ECLA group had returned
to work. Even though both groups
had close-to-normal and similar-
to-baseline pulmonary function test
Parts of this article appeared in the October
2013 issue of the Society of Critical Care
Medicine’s Clinical Pharmacy and Pharmacol-
ogy Section Newsletter.
The authors have declared no potential
conflicts of interest.
Copyright © 2015, American Society of
Health-System Pharmacists, Inc. All rights
reserved. 1079-2082/15/0801-1315.
DOI 10.2146/ajhp140533
1315
 COMMENTARIES  Postintensive care syndrome
results, 75% of the ECLA group and
64% of the non-ECLA group had
reduced diffusion capacity across
the blood-gas barrier as well as some
exercise limitations.
Physical functions at 6 and 12
months after ARDS were evaluated
in the EDEN trial, a large multicenter
study examining initial trophic ver-
sus full enteral feedings in patients
with ARDS.8 Patients had substantial
impairments, as demonstrated by
mean ± S.D. six-minute walk distanc-
es of 64% ± 22% and 67% ± 26% of
predicted values at 6 and 12 months,
respectively, and SF-36 physical func-
tion scores of 61% ± 36% and 67% ±
37% of predicted values at 6 and 12
months, respectively.
Together, the results of these
studies illustrate the degree of re-
covery seen in patients 12 months
after ARDS, with impairments in six-
minute walk test values and test re-
sults evaluating physical function, as
well as persisting symptoms of dysp-
nea and inability to return to work,
without substantial further improve-
ment in pulmonary function beyond
that seen at 12 months.
Posttraumatic stress disorder.
Posttraumatic stress disorder (PTSD)
occurs in 5–64% of patients after
ICU discharge.9 Patients with PTSD
may be left with vivid flashbacks of
memories of painful procedures or
delirious hallucinations as well as
symptoms of anxiety and depression
lasting months to years after recovery
from the illness that led to their ICU
stay.10 A recent New York Times article
highlighted the occurrence of PTSD
after ICU hospitalization, recounting
stories of patients who experienced
disturbing hallucinations during the
course of their stay.11
A prospective, single-center co-
hort study was conducted in 194 pa-
tients one year after discharge from
a medical, surgical, or trauma ICU
to evaluate the frequency of PTSD
using the Impact of Event Scale
(IES).10 The IES has two subscales
(measuring intrusion and avoidance)
1316 Am J Health-Syst Pharm—Vol 72 Aug 1, 2015
that directly correspond to 14 of 17
Diagnostic and Statistical Manual of
Mental Disorders, 4th Edition, criteria
for PTSD. The intrusion subscale
contains 7 items, and the avoidance
subscale contains 8 items. Each item
can receive a score of 0 to 5, with the
total IES score ranging from 0 to 75.
More-severe PTSD symptoms are as-
sociated with higher scores. A score
of >20 is indicative of clinical rel-
evance, while a score of >35 reflects
severe symptoms. The mean IES
score was 22.5 (95% confidence in-
terval [CI], 20–25.1) at one year after
ICU discharge. Forty-eight patients
(28% of 180) had scores of >35.
Mean IES scores did not significantly
differ between assessments per-
formed at 4–6 weeks, 3 months, or 12
months after discharge (p = 0.388).
Categorization of patients into their
respective services (medical, surgi-
cal, or trauma ICU) did not result
in a difference in the rates of PTSD,
depression, or anxiety. The following
characteristics were found to be inde-
pendent predictors of PTSD one year
after ICU discharge: high educational
level (odds ratio [OR], 0.4; 95% CI,
0.2–1.0), optimism (OR, 0.9; 95% CI,
0.8–1.0), factual recall of events (OR,
6.6; 95% CI, 1.4–31.0), and memory
of being in pain (OR, 1.5; 95% CI,
1.1–2.0).
An additional prospective cohort
study evaluated 78 mixed trauma–
surgical patients to determine the
frequency and severity of PTSD
symptoms three months after ICU
discharge. 12 Fourteen percent of
patients met the criteria for PTSD
based on the Davidson Trauma Scale.
The score was inversely correlated
with age and directly associated with
length of time on a ventilator.
Cognitive impairment. Cognitive
impairment is another morbidity
related to multiorgan dysfunction,
hypotension, and hypoxemia; it
may be secondary to illnesses such
as ARDS and severe sepsis and can
be a consequence or manifesta-
tion of ICU delirium.13-15 Cognitive
impairment in the ICU setting can
be thought of as acute brain dysfunc-
tion, and long-term ICU stays may
impair functioning and have psycho-
logical consequences that drastically
interfere with the ability of patients
to return to routine, daily activities.16
Neurocognitive impairment may
involve the domains of executive
functioning, memory, and attention,
leading to difficulties with planning,
problem solving, and behavioral
control.15,17 Not surprisingly, impair-
ments in cognition may also be as-
sociated with psychological dysfunc-
tion such as anxiety and depression.18
An a priori analysis assessing cog-
nitive function at 3 and 12 months
after discharge was conducted in 180
medical ICU patients at one center
during the Awakening and Breathing
Controlled (ABC) Trial, which com-
pared paired spontaneous awakening
trials and breathing trials (interven-
tion group) to standard sedation
practices and spontaneous breathing
trials (control group).19 Cognitive
impairment was less common in the
intervention group at 3 months after
discharge compared with the con-
trol group (absolute risk reduction,
20.2%; 95% CI, 1.5–36.1%; p = 0.03)
but did not significantly differ at 12
months after discharge. Although
this study did not demonstrate the
long-term persistence of cognitive
dysfunction found in other studies,
the ABC Trial countered the tradi-
tional belief that deep sedation was
necessary to prevent the adverse psy-
chological consequences of mechani-
cal ventilation and showed that deep
sedation may in fact be harmful by
impeding extubation and prolonging
hospitalization.20
The duration of delirium during
hospitalization may also be associ-
ated with long-term cognitive im-
pairment and was studied prospec-
tively in 77 patients who required
mechanical ventilation during a
medical ICU admission.21 Patients
were assessed daily for delirium
while in the ICU (median duration

of delirium, two days. Three months
after discharge, 79% of patients had
cognitive impairment, with 62% hav-
ing severe cognitive impairment. One
year after discharge, 71% of patients
had cognitive impairment, 36% of
whom were classified as severely im-
paired. The duration of delirium was
determined to be an independent
risk factor for worse cognitive func-
tion by averaging age-adjusted and
education-adjusted T scores from
nine tests assessing cognition after
adjusting for age, education, baseline
cognitive function, illness severity,
and use of sedatives in the ICU.
Cognitive dysfunction in nondelir-
ious patients has also been evaluated.
The Cambridge Neuropsychological
Test Automated Battery (CANTAB)
was used to evaluate 16 long-term
ventilated ICU patients for cognitive
impairment in the Netherlands. 18
Two months after discharge, 5 (31%)
of the 16 patients scored lower than
the 25th percentile for memory, and
8 of the 16 patients (50%) scored
lower than the 25th percentile for
problem solving.
In 2005, Hopkins and colleagues
specifically studied long-term out-
comes in the ARDS population.22 A
total of 128 patients were selected
from a larger ARDS Network study
and randomized to receive low or
high tidal volume ventilation for
the treatment of ARDS. 22,23 The
authors assessed cognitive function
and found that 46% and 47% of
patients demonstrated neurocogni-
tive dysfunction one and two years
after discharge, respectively.22 This
finding was corroborated by the
aforementioned EDEN study, which
found that 36% of survivors had cog-
nitive impairment at 6 months and
25% had cognitive impairment at 12
months after discharge (p = 0.001).8
Finally, the recent Bringing to
Light the Risk Factors and Incidence
of Neuropsychological Dysfunction
in ICU Survivors (BRAIN-ICU)
study has shed more light onto the
significance of the impact of critical
COMMENTARIES  Postintensive care syndrome
care hospitalization on long-term
cognition.24 This multicenter, pro-
spective, observational cohort study
of 821 adult medical ICU and sur-
gical ICU patients with respiratory
failure, cardiogenic shock, or septic
shock was conducted to estimate the
rates of long-term cognitive impair-
ment after critical illness. Over 50%
of these patients had cognitive im-
pairment following their stay in the
ICU, with delirium being the largest
predictive factor. Forty percent of pa-
tients had a Repeatable Battery for the
Assessment of Neuropsychological
Status (RBANS) score worse than
that usually observed in patients with
moderate traumatic brain injury (1.5
standard deviations below the popu-
lation mean), and an RBANS score
similar to that typically observed in
patients with Alzheimer’s disease (2
standard deviations below the popu-
lation mean) was found in 26% of
patients at 3 months after discharge.
At 12 months after follow-up, 34%
of patients age 49 years or younger
had RBANS scores similar to those
associated with moderate traumatic
brain injury, and 20% had scores
similar to those of patients with mild
Alzheimer’s disease.
According to the results of the
above studies, serious neurocogni-
tive impairment after hospitalization
is prevalent in a variety of general
ICU populations and persists in the
long-term for years after discharge.
Potential areas for improvement in
care include interventions such as
the coordination of spontaneous
awakening and breathing trials to
reduce exposure to sedating medica-
tions and shorten the time spent on
mechanical ventilation, as well as
methods to prevent and reduce the
duration of delirium in ICU patients.
Currently, post-ICU care mainly fo-
cuses on physical rehabilitation and
neglects to address the possibility for
psychological or cognitive recovery
of patients.11 Now that evidence has
shown the widespread occurrence of
these impairments, it is clear that a
Am J Health-Syst Pharm—Vol 72 Aug 1, 2015
holistic approach to the treatment of
ICU survivors to improve their qual-
ity of life (QOL) is necessary.
Decreased QOL. Patients who sur-
vive ARDS have been found to have
a decreased QOL during the first
year after discharge. The previously
mentioned study by Hopkins and
colleagues22 assessing the long-term
outcomes of ARDS survivors also
evaluated QOL using the SF-36 at
one and two years after discharge.
Repeated-measures analysis of vari-
ance was used to evaluate the SF-36
scores and showed a significant dif-
ference in domain scores over time
(F[2,102] = 8.9, p < 0.001). Scores
for domains related to physical and
social functioning, “role physical,”
and vitality were decreased at hospi-
tal discharge. Although these scores
improved during the first year, no
additional improvement was seen at
two years. Scores for domains related
to “role emotional,” pain, and general
health did not change from hospital
discharge to the two-year follow-up
endpoint. Mental health domain
scores did improve during the first
year but decreased to the hospi-
tal discharge level at the two-year
follow-up endpoint.
In another study, 73 survivors of
ARDS were assessed at 3, 6, and 12
months to evaluate health-related
QOL and lung spirometry tests.25
ARDS survivors had lower values
than age- and sex-matched popula-
tion scores at all three time points
using the SF-36 and St. George’s
Respiratory Questionnaire (SGRQ).
Significant improvement was seen
in the physical component score
at the 12-month evaluation point.
However, 57% of individuals evalu-
ated had not returned to their
baseline activity level at 12 months,
as assessed by measuring physical
performance. In addition, the men-
tal domain scores on the SF-36 and
SGRQ did not differ significantly
from baseline. Stable, mild abnor-
malities were found on lung spirom-
etry tests at 12 months. There was a
1317
 COMMENTARIES  Postintensive care syndrome
strong correlation between the FEV1
value and the score on the physical
function domain of the SF-36 (cor-
relation coefficient, 0.601; p < 0.01).
A moderate correlation was also seen
between the FEV1 value and the score
on the SGRQ domains (correlation
coefficients, –0.36, –0.5, –0.5, –0.5;
p < 0.01 for all domains).
A meta-analysis was conducted to
summarize measured QOL in ARDS
survivors at least 30 days after ICU
discharge.26 Thirteen studies includ-
ing a total of 557 patients were evalu-
ated. Five studies used the SF-36 to
measure QOL (n = 330). The mean
scores for QOL were similar among
these 5 studies. After evaluating spe-
cific domains at six months or later
after ICU discharge, SF-36 scores
were 15–26 points lower than popu-
lation comparators. Only 1 of the
original 13 studies found significant
improvement in QOL six-months
following discharge, but 6 of the 13
studies found stable or improved
QOL as time passed after discharge.
Decreased QOL is not limited to
patients recovering from ARDS. A
prospective, one-year follow-up study
was conducted to evaluate differences
in health-related QOL in patients after
discharge from a medical, surgical, or
trauma ICU.27 Significantly lower
SF-36 scores for health-related QOL
were found among these patients
compared with the general population
at one year after discharge (p < 0.001).
For the physical domain, multivari-
ate regression analyses identified the
following independent risk factors:
optimism, medical disease, length of
ICU stay, employment status before
the ICU stay, and PTSD symptoms
(beta, –9.1; p < 0.05 for all; adjusted r =
0.22). Independent predictors of the
mental health domain were optimism,
employment status before ICU stay,
and PTSD symptoms (beta, –11.6; p <
0.001 for all; adjusted r2= 0.35).
Approaches to improve out-
comes. Inpatient rehabilitation. A
study conducted at two university
hospitals enrolled 104 adult patients
1318 Am J Health-Syst Pharm—Vol 72 Aug 1, 2015
who had been mechanically ven-
tilated for less than 72 hours, were
expected to remain intubated for
at least an additional 24 hours, and
were functionally independent at
baseline.28 Patients were random-
ized to early exercise and mobiliza-
tion during the daily interruption
of sedation (n = 49) or therapy as
ordered by the primary healthcare
team (n = 55). A return to indepen-
dent functional status at hospital
discharge, defined as the ability to
perform six activities of daily living
and walk independently, occurred
in 29 patients in the early mobiliza-
tion group (59%) versus 19 in the
standard therapy group (35%) (p =
0.02; OR, 2.7; 95% CI, 1.2–6.1). In
addition, a significantly shorter du-
ration of delirium was found in the
early mobilization group (median
duration, 2 days; interquartile range
[IQR], 0–6 days) compared with the
standard therapy group (median
duration, 4 days; IQR, 2–8 days) (p =
0.02). The early mobilization group
also had more ventilator-free days
(median, 23.5 days; IQR, 7.4–25.6
days) compared with the standard
therapy group (median, 21.1 days;
IQR, 0–23.8 days; p = 0.05). Only
one serious adverse event (oxygen
desaturation to less than 80%) oc-
curred during the total 498 therapy
sessions administered during the
study. Nineteen patients had therapy
discontinued due to presumed asyn-
chrony with the ventilator.
The Activity and Cognitive
Therapy in ICU (ACT-ICU) trial
was a single-center feasibility study
that randomized 87 medical or
surgical ICU patients with shock or
respiratory failure in a 1:1:2 ratio to
usual care (n = 22), early once-daily
physical therapy (n = 22), or early
once-daily physical therapy plus
twice-daily cognitive therapy (n =
43).29 Cognitive therapy in nonco-
matose patients involved orienta-
tion, memory, and attention exer-
cises (e.g., forward- and reverse-digit
spans, matrix puzzles, letter–number
sequences, pattern recognition);
physical therapy ranged from passive
range-of-motion exercises to walking
and activities of daily living train-
ing. Ninety-five percent of patients
randomized to the physical therapy
plus cognitive therapy group received
early cognitive therapy on 100%
of study days. Physical therapy was
conducted with 77% of patients in
the usual care group on 17% of study
days, 95% of patients in the physical
therapy group on 67% of study days,
and 98% of patients in the physical
therapy plus cognitive therapy group
on 75% of study days. After three
months, no significant difference was
found among groups in measures of
executive function (Tower Test and
Dysexecutive Questionnaire), glob-
al cognition (Mini-Mental Status
Exam), functional mobility (Timed
Up-and-Go Test), activities of dai-
ly living (Katz Activities of Daily
Living), instrumental activities of
daily living (Functional Activities
Questionnaire), or health-related
QOL (European Quality of Life–5
Dimensions Visual Analog Scale).
Further, there was no significant
difference found among groups
in delirium- or coma-free days,
ventilator-free days, length of ICU
stay, and length of hospital stay.
Although this feasibility study did
not find any significant differences in
outcomes among the groups, it did
reveal that implementing a combined
program of physical and cognitive
therapy was possible, with physical
therapy being received by 95–98%
of intervention patients, compared
with 77% of patients in the usual care
group. However, additional research
needs to be conducted in a larger
patient population to assess the true
beneficial impact on long-term out-
comes in critically ill patients.
Postdischarge cognitive and physi-
cal rehabilitation. A single-center fea-
sibility study (Returning to Everyday
Tasks Utilizing Rehabilitation
Networks [RETURN]) followed 21
medical and surgical ICU patients

with cognitive or functional impair-
ment at hospital discharge to assess
usual care (sporadic rehabilitation)
with in-home combination therapy
including cognitive, physical, and
functional therapy.30 Cognitive, ex-
ecutive functioning was improved
as assessed by the Tower Test in the
intervention group (median score,
13; IQR, 11.5–14.0) compared with
the usual care group (median score,
7.5; IQR, 4.0–8.5; p < 0.01) at three
months. Further, patients in the in-
tervention group (median score,
1; IQR, 0–3) also achieved better
scores on the Functional Activities
Questionnaire at three months as
compared with the usual care group
(median score, 8; IQR, 6.0–11.9; p =
0.04). Larger studies are needed to
further validate these results.
ICU diaries. The use of a diary
is one way to potentially fill in the
memory gaps for patients and to
also facilitate psychological recovery.
Although there is not a standard
practice regarding the content of
the diary or how the diary is used,
in most cases a diary is prospectively
initiated by either a nurse or a fam-
ily member and updated throughout
the patient’s stay to document the
course of the hospital stay and to
recount events and emotions that the
patient may not be able to recount
after the hospital stay. By adding a
factual narrative to the likely seeming
string of disconnected events, mem-
ories, and dreams, the use of diaries
may help the process of recovery for
patients and their family members.31
Amnesia is one of the most troubling
consequences of critical illness, and
anecdotal reports have highlighted
the potential of using diaries to aid
patients in adjustment to their recov-
ery state and understanding of their
illness course.32 ICU diary usage is
the highest in Scandinavia and the
United Kingdom, and diaries are
most commonly given to patients
who are mechanically ventilated
or sedated for a prolonged period
of time. Contents of these diaries
COMMENTARIES  Postintensive care syndrome
include the admission diagnosis, a
daily activity summary, and a note
when the patient is discharged from
the ICU.33
One prospective cohort study and
two randomized controlled trials
in addition to observational stud-
ies have evaluated the effects of ICU
diaries on medical outcomes. In a
nonrandomized prospective study,
the health-related QOL of 38 patients
who received an ICU diary with pho-
tographs was compared with a group
of ICU patients who did not receive
the diary (n = 224) at 6, 12, 24, and 36
months after hospital discharge.34 The
intervention group was found to have
significantly higher SF-36 scores for
general health and vitality compared
with the control group (p < 0.05), and
some of these effects were sustained at
3 months after discharge (p < 0.05).
A randomized study including
352 patients was conducted in 12
European ICUs.35 Patients were given
a diary and photographs one month
after ICU discharge. The frequency
of new cases of PTSD was lower in
the intervention group compared
with the control group using the
PTSD Diagnostic Scale (3% versus
13%, p = 0.02). However, no dif-
ference was found between groups
using the Post-Traumatic Stress
Syndrome 14 screening tool at one
and three months, and no improve-
ment was found between assessments
conducted at one and three months
postdischarge.
The second randomized study
evaluated 36 patients in an ICU in
the United Kingdom.32 A diary was
prepared by ICU staff and was re-
viewed with patients in the interven-
tion group approximately one month
after discharge with an ICU nurse
consultant. During the verbal feed-
back session, the nurse also answered
patients’ questions about the diary
and events that occurred. Significant
decreases in anxiety (p < 0.05) and
depression (p < 0.005) were found
in the intervention group compared
with the control group.
Am J Health-Syst Pharm—Vol 72 Aug 1, 2015
While positive effects of ICU dia-
ries were observed in these studies,
further large studies with a broader
sample utilizing standardized assess-
ment and evaluation methods are
needed to provide more robust data
to support routine ICU diary imple-
mentation. However, because of the
lack of harm demonstrated, this
practice may be reasonably imple-
mented at this time.
Transitions of care. Over the past
decade, it has become evident that
there is a substantial risk for adverse
drug events (ADEs) during transi-
tions of care. ADEs can occur at any
time, but they are most likely to occur
during transitions of care. A transition
of care has been defined as any time a
patient has a change in provider (e.g.,
from an ICU to a general ward, from a
hospital to a long-term care facility).36
Many hospital readmissions and
emergency room visits after discharge
are medication related.
In one study, readmissions oc-
curred in 20% of Medicare recipients
within 30 days of discharge and in
34% within 90 days of discharge.37 A
posthospitalization visit to a primary
care provider did not occur in about
one half of the patients who were
readmitted within 30 days of dis-
charge, and a lack of understanding
of home and discharge medications
was found to be a contributing fac-
tor to readmission. Patients taking
more than five medications daily
or those with cognitive impairment
are examples of specific populations
at increased risk for an ADE during
transitions of care.36
A recent single-center study evalu-
ated the frequency of potentially
inappropriate medications (PIMs)
and actually inappropriate medica-
tions (AIMs) prescribed for 120
elderly ICU survivors.38 PIMs were
defined as medications that are
potentially harmful based on prior
research and knowledge of pharma-
cologic effects; PIMs could then be
classified as AIMs when consider-
ing the risk:benefit ratio in light of
1319
 COMMENTARIES  Postintensive care syndrome
the patient’s clinical circumstances.
These assessments of each individual
patient’s medication lists were made
according to the 2003 Beers criteria
and other newer published scales at
five distinct points during the hospi-
tal stay: admission, ward admission,
ICU admission, ICU discharge, and
hospital discharge. Opioids, anticho-
linergic medications, antidepres-
sants, and drugs causing orthostasis
were the most common categories
of PIMs identified at discharge;
36% of these PIMs were considered
to be AIMs via assessment by the
clinical panel. The positive predic-
tive value was also calculated to
describe the number of PIMs that
were subsequently determined to
be AIMs. At discharge, the PIM
categories with the highest positive
predictive value for AIMs included
anticholinergics (55%), nonbenzo-
diazepine hypnotics (67%), benzo-
diazepines (67%), atypical antipsy-
chotics (71%), and muscle relaxants
(100%). Multivariate analysis found
that the number of discharge PIMs
was independently predicted by the
number of preadmission PIMs (p <
0.001), discharge to somewhere other
than home (p = 0.03), and discharge
from a surgical service (p < 0.001).
Another important study finding
was that nearly two of every three
AIMs were initiated in the ICU. It
is likely that many of these medica-
tions initiated in the ICU or at any
other time during the hospital stay
may have been appropriate for tem-
porary or short-term use based on
the patient’s clinical situation, but the
failure to discontinue such medica-
tions beyond that time period results
in inappropriate and prolonged use.
For example, only 12% of patients
were taking an anticholinergic before
admission, but 37% of patients were
discharged on a medication in this
class.38
In addition to the continuation
of unnecessary PIMs after hospital
discharge, there also exists the pos-
sibility for errors of omission from
1320 Am J Health-Syst Pharm—Vol 72 Aug 1, 2015
discharge medication lists. A large
population-based cohort study con-
ducted in Canada examined the
records of hospital and outpatient
prescriptions of nearly 400,000 pa-
tients age 66 years or older for whom
a medication from at least one of the
five following groups for treatment
of a chronic condition was pre-
scribed: (1) statins, (2) antiplatelet
or anticoagulant agents, (3) levothy-
roxine, (4) respiratory inhalers, and
(5) gastric-acid–suppressing drugs.39
Patients were then separated accord-
ing to hospitalization in an ICU,
hospitalization without ICU admis-
sion, and nonhospitalized patients
(controls). The authors compared
rates of medication discontinuation
among these three groups and found
that patients admitted to a hospital
were significantly more likely to have
medications discontinued among
all five of the medication groups;
adjusted ORs ranged from 1.18 (95%
CI, 1.14–1.23) for discontinuation
of levothyroxine to 1.86 (95% CI,
1.77–1.97) for discontinuation of
antiplatelet or anticoagulant agents.
Among patients specifically admit-
ted to an ICU, there was a higher
risk of medication discontinuation
in all medication groups except for
respiratory inhalers when compared
with patients hospitalized without
an ICU admission. The secondary
outcome of the composite risk of
death, hospitalization, and emer-
gency department visit up to one
year after hospital discharge in the
entire study population was signifi-
cantly higher in patients for whom a
statin or antiplatelet or anticoagulant
agent was discontinued. Although
the retrospective nature of this study
did not allow for the adjudication of
reasons for discontinuation (indeed,
reasons for discontinuation may have
been appropriate according to the
reason for hospitalization or hospital
course), the study did highlight the
likelihood that medication discon-
tinuations during the course of a
hospitalization will lead to errors of
omission in the patient’s discharge
medication list.
In light of this mounting litera-
ture, the Joint Commission in 2011
declared “sustaining and properly
communicating correct medication
information” to be a new National
Patient Safety Goal.40 Pharmacists
are clearly a professional group who
should hold accountability for this,
though responsibility will always be
shared with all healthcare provid-
ers. Having a unique set of skills
and positions of access to patients
allow pharmacists to be the optimal
individuals to review patient medica-
tion lists and medical diagnoses and
rectify missing or extraneous medi-
cations during transitions of care,
especially at discharge. The above
studies demonstrated that patients
are often not making contact with
primary care providers as instructed
after discharge, making discharge
reconciliation and counseling by the
pharmacist even more important.
Knowledge of therapeutics and dis-
ease management allows pharmacists
to recognize the highest-risk patient
populations for intervention, such as
the elderly.
Post-ICU clinics. Other parts of
the world have been more progres-
sive in recognizing the importance of
the transition for patients after ICU
stays. While ICU follow-up clinics
are a novelty in the United States,
the concept emerged in the United
Kingdom 20 years ago, with one of
the first established in 1993.41 Named
“Intensive after Care after Intensive
Care,” the service sees patients in
clinics for half a day twice a month
and is run jointly by a nurse and an
ICU consultant. Patients who were in
the ICU for at least four days are seen
at 2, 6, and 12 months after discharge.
Within 15 years after this clinic was
created, several more clinics had been
opened within the United Kingdom.
All of these ICUs were surveyed
in 2006 to characterize the state
of ICU follow-up clinics around
the country.42 Of the 298 ICUs in

existence at the time, 80 (30%) of 266
responding ICUs ran post-ICU clin-
ics. Of these, 55% were led by nurses,
and 77% invited only patients with
ICU stays of three to four days or
longer. Approximately one third of
the clinics had prenegotiated access
to psychology and physical therapy
services for their patients, indicat-
ing involvement in interprofessional
care. Clinics of this type have also
been described in Australia.43
Another study conducted in the
United Kingdom prospectively com-
pared a program of intervention to
a clinic run by nurses to evaluate
the impact on health-related QOL,
measured by the SF-36, in the year
after ICU discharge.44 Three hospi-
tals enrolled 286 patients who were
randomized in an unblinded fashion
to participate in a manual-based,
self-directed physical rehabilitation
program or to receive the standard of
care (i.e., follow-up customary with
primary care providers). Patients in
the intervention group were seen at
the nurse-led clinic at three and nine
months after their ICU stay. During
clinic visits, patients discussed their
experiences of their critical illness,
underwent psychological screening,
and were assessed for specialist refer-
ral. Disappointingly, this study failed
to find an improvement in health-
related QOL between the two study
groups. Some limitations include the
fact that all patients admitted to an
ICU, regardless of length of stay, were
included and that all tests of cogni-
tive ability and physical and pulmo-
nary functions as well as medication
reviews were performed by the clinic
nurse. Patients were not seen by spe-
cialists in these fields unless referred.
Because of the relative lack of ro-
bust published data assessing the op-
timal combination of services in such
clinics or the outcomes of patients
treated at ICU follow-up clinics, it
is still unknown if or which specific
subgroups of patients are most in
need of continuity of care after ICU
hospitalization and would benefit the
COMMENTARIES  Postintensive care syndrome
most. It is also unknown how soon or
how often patients might need to be
seen at follow-up clinics to have the
greatest impact on outcomes.45
Primary care providers may not
be equipped with an understanding
of specific critical care issues and the
tools to assess or manage them. Many
must frequently make referrals to
other disciplines, which may poten-
tially compromise the patient’s likeli-
hood of seeking out and receiving all
of the healthcare services required
to optimize his or her recovery. The
pharmacist and team of ICU clinic
members are specialized in under-
standing the toll of intensive care hos-
pitalization. With knowledge of the
patient’s specific hospital course, they
can use their expertise to manage care
in an interprofessional manner.
According to the post-ICU com-
plications previously cited, the fol-
lowing individuals should be consid-
ered for involvement in the post-ICU
clinic: physicians, psychologists,
physical therapists, respiratory ther-
apists, social workers, palliative
care specialists, and pharmacists.
Assessments made during the clinic
visit should include progress in phys-
ical rehabilitation; ability to perform
activities of daily living and the need
for occupational therapy; evaluation
of pulmonary function tests; assess-
ment of cognitive function and the
presence of mental health issues such
as depression, PTSD, and anxiety;
medication therapy review, reconcili-
ation, and counseling; and coordina-
tion of care and communication with
primary care providers and other
specialists as needed.
In the ICU follow-up setting, the
pharmacist is able to play a unique
role in transitioning the patient’s
care, combining the role of both the
inpatient and outpatient pharmacist.
The pharmacist has the ability to
perform all aspects of the complete
medication-use process, including
medication reconciliation (appen-
dix). Before the clinic visit, prepara-
tion may consist of reviewing the
Am J Health-Syst Pharm—Vol 72 Aug 1, 2015
patient’s medical chart and discharge
medication list. A problem list may
be copied from the chart or created
in preparation for medication ther-
apy review, as well as any pertinent
laboratory test results that may be
assessed or those that may be needed.
Communication between the patient
and the clinic coordinator in plan-
ning the clinic visit may also identify
any specific complaints the patient
has that may have prompted him or
her to make the appointment, which
may be helpful in the pharmacist’s
previsit workup.
A comprehensive review of medi-
cations should be done to ensure that
each is appropriate and indicated.
This component requires medica-
tion reconciliation skills, which may
involve evaluating the patient’s medi-
cation list before hospitalization,
during hospitalization including
transitions between units, at dis-
charge, and as currently reported by
the patient. Any differences should
be identified and reconciled. The
patient interview should also assess
for adverse effects of medications
as well as any residual effects of the
ICU stay, such as pain, fatigue, or
insomnia. Once medications are
reconciled, patient counseling will
include a review of all medications,
including nonprescription medica-
tions, which would ideally entail a
review of the indications, how to take
the medication, the adverse effects,
and monitoring. Effective counsel-
ing includes an assessment of patient
adherence with medication therapy
and identification of any barriers to
accessing or obtaining medications.
Often, coordination may be needed
between other healthcare providers,
including the other members of the
ICU clinic, the patient’s primary care
physician or other specialty provid-
ers, and the community pharmacist.
Future directions in post-ICU
care. Post-ICU care is becoming an
increasingly common area of inter-
est and research. The concept of the
post-ICU clinic is being considered
1321
 COMMENTARIES  Postintensive care syndrome
in the United States, as more focus
is placed on quality improvement
in transitions of care. In the post-
ICU care setting, pharmacists can
aid in the transition from hospital
to community, potentially increase
adherence and patient understand-
ing of medications, promote patient
acquisition of medications, and de-
crease the occurrence of ADEs and
drug–drug interactions. To date, no
studies have determined if the care
provided in multidisciplinary post-
ICU clinics results in a decrease
in hospital readmissions. Future
studies should attempt to identify
patients who will benefit the most
from follow-up in post-ICU clinics
as well as the optimal time frame for
interventions.
Conclusion. Long-term conse-
quences of ICU hospitalization may
include impaired pulmonary func-
tion, PTSD, cognitive impairment,
and decreased QOL. Approaches to
improve outcomes in patients requir-
ing ICU admission may involve in-
patient rehabilitation, postdischarge
cognitive and physical rehabilitation,
use of ICU diaries, interprofessional
care coordination during transitions
of care, and implementation of post-
ICU clinics.
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Appendix—Pharmacist’s role in the
intensive care unit (ICU) follow-up clinic
visit
Before clinic visit
• Review patient chart for medical history, hos-
pital course, medications, and other data
Medication reconciliation
• Compare medication lists before hospital-
ization, at discharge, and at the time of the
follow-up visit
• Reconcile and investigate reasons for any
differences among these lists, such as medica-
tions without indications not discontinued
during hospitalization, errors of omission
Am J Health-Syst Pharm—Vol 72 Aug 1, 2015
(medications not restarted), and nonprescrip-
tion medications
Medication therapy review
• Match indications and problem list with
medications after medication reconciliation is
performed
Patient interview
• Identify presence of any adverse medication
effects
• Review patient complaints and problem list
that may indicate need for pharmacologic or
nonpharmacologic intervention
Patient counseling
• Review medications with the patient (indica-
tion, directions, adverse effects, monitoring)
Assessment
• Review barriers to accessing or obtaining
medications
• Promote adherence with medication regimens
• Order any pertinent laboratory tests to be
performed
Conclusion of visit
• Discuss medications to be discontinued, initi-
ated, or reinitiated with the team and with the
patient
• Discuss appropriate follow-up coordination
(return visit to ICU clinic or other appropri-
ate provider such as primary care provider,
communication with community pharmacist,
methods for obtaining medications)
1323