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Department of Anesthesiology, Box 1010 Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029-6574, United States
Department of Surgery, Box 1010 Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029-6574, United States
c
Department of Geriatrics and Palliative Care, Box 1010 Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029-6574, United States
d
Department of Neurosurgery, Box 1010 Mount Sinai School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029-6574, United States
e
Outcomes Research Consortium, Cleveland, Ohio, United States
b
a r t i c l e
i n f o
Article history:
Received 31 May 2012
Received in revised form 10 November 2012
Accepted 11 November 2012
Available online 6 December 2012
Keywords:
Dementia
Long term cognitive impairment
Postoperative cognitive dysfunction
Postoperative delirium
a b s t r a c t
A number of serious clinical cognitive syndromes occur following surgery and anesthesia. Postoperative delirium is a
behavioral syndrome that occurs in the perioperative period. It is diagnosed through observation and characterized
by a uctuating loss of orientation and confusion. A distinct syndrome that requires formalized neurocognitive
testing is frequently referred to as postoperative cognitive dysfunction (POCD). There are serious concerns as to
whether either postoperative delirium or postoperative cognitive dysfunction leads to dementia. These concerns
are reviewed in this article.
2012 Elsevier Inc. All rights reserved.
Contents
1.
Introduction
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.
What is delirium? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.
What is dementia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.
What is (are) Post Operative Cognitive Dysfunction (POCD) and Long Term Cognitive Impairment (LTCI)?
5.
Relationship of symptomatology/overlap in diagnosis . . . . . . . . . . . . . . . . . . . . . . . .
6.
Relationship of pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7.
Pathophysiology of POCD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8.
Does delirium lead to POCD/LTCI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9.
Does surgery and anesthesia impact the incidence or trajectory to AD? . . . . . . . . . . . . . . . .
10.
Does postoperative delirium lead to dementia? . . . . . . . . . . . . . . . . . . . . . . . . . . .
11.
Does dementia cause delirium?
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
12.
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction
Since the 1950s, it has been clear that patients undergoing surgery
and anesthesia suffer from postoperative cognitive changes. Two
distinct syndromes have been described. Postoperative delirium is
Abbreviations: POCD, postoperative cognitive dysfunction; LTCI, Long Term Cognitive Impairment.
Corresponding author at: Department of Anesthesiology, Box 1010 Mount Sinai
School of Medicine, 1 Gustave L. Levy Place, New York, NY 10029-6574, United
States. Tel.: + 1 212 241 7749; fax: + 1 212 876 3906.
E-mail address: jeff.silverstein@mssm.edu (J.H. Silverstein).
0278-5846/$ see front matter 2012 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.pnpbp.2012.11.005
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J.H. Silverstein, S.G. Deiner / Progress in Neuro-Psychopharmacology & Biological Psychiatry 43 (2013) 108115
109
Delirium
Hypoac
ac Hypera
ctiv
ctive
ve
tive
Subsyn
dromal
Dementia
Anesthesia
Neurotoxicity
Inflammation
Stress
Surgery
POCD/LTCI
Cognitive
Reserve
CoMorbid
Conditions
Intercurrent
Events
Fig. 1. Potential relationships between anesthesia, surgery and the ultimate development of long term cognitive impairment. This conception indicates that neurotoxicity, inammation and stress appear to be the mediators of both delirium and LTCI. Delirium may represent an intermediate step on the road to LTCI for some patients. Other conditions such as
pre-existing impairment (lack of cognitive reserve), co-morbid illness and intercurrent events (e.g. postoperative complications) may also play a role in the development of these
problems.
2. What is delirium?
Delirium is a neuropsychological syndrome characterized by disorganized thinking, lack of orientation and a uctuating course. Delirium has become a focal point for much recent study and the
formation of specialty societies in both Europe and the United States
Table 1
DSM V delirium (with notes regarding alteration of denitions from the DSM IV).
A. Disturbance in level of awareness and reduced ability to direct, focus, sustain, and shift attention (this represents a minor change from: Disturbance of consciousness (i.e., reduced clarity of awareness of the environment) with reduced ability to focus, sustain or shift attention).
B. A change in cognition (such as decits in orientation, executive ability, language, visuoperception, learning and memory).
- Cannot be assessed in face of severely reduced level of awareness
- Should not be better accounted for by a preexisting neurocognitive disorder
(A minor change from a change in cognition or the development of a perceptual disturbance that is not better accounted for by a preexisting, established or evolving dementia.)
C. There is evidence from the history, physical examination, or laboratory ndings that the disturbance is caused by the direct physiologic consequences of a general medical condition (no change from DSM IV).
D. The disturbance develops over a short period of time (usually hours to a few days) and tends to uctuate in severity during the course of a day (no change from DSM IV).
Clouding of consciousness
Impairment of attention
Perceptual disturbance
Disorganized thinking/speech
Disturbance of sleep
Motor activity change
Disorientation
Memory impairment
Impairment of abstract thinking or comprehension
Emotional disturbance
Rapid onset and uctuating symptoms
Causative factor
ICD-10
DSM-II
DSMII-R
DSM IV
DSM V
NPI
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
110
J.H. Silverstein, S.G. Deiner / Progress in Neuro-Psychopharmacology & Biological Psychiatry 43 (2013) 108115
(MacLullich and Hall, 2011). The basis for the concerns about delirium includes the additional difculty and cost associated with the
care of individuals who develop delirium, the association of delirium
with other complications, increasing morbidity and mortality, and
the concern about its relationship to POCD and dementia (Leslie and
Inouye, 2011; Rudolph and Marcantonio, 2011).
The denition of delirium has evolved over recent years. The
Diagnostic and Statistical Manual of the American Psychiatric Association represents the consensus denition for most psychiatric conditions. The current proposal for the DSM V is listed in Table 1. As this
represents a minor change from the DSM IV-TR, Table 1 also notes the
alterations from the previous denition. It is important to appreciate
that delirium is a behavioral syndrome that is diagnosed by observing
a patient. The primary instruments for diagnosis of delirium, the
Confusion Assessment Method (CAM) (Wei et al., 2008) and the
Delirium Rating Scale (DRS) are not interchangeable (Trzepacz et
al., 2001). There is considerable variation in how the instruments
are utilized. Some groups use multiple instruments to inform the
CAM and others use short interviews. There are alternative versions
and foreign language versions of both.
Postoperative delirium is a specic subset of the panorama of deliria.
Two different syndromes are discussed but only one is consistent with
the classic denition of delirium (Deiner and Silverstein, 2009). Upon
the cessation of general anesthesia, is it somewhat common for patients
to be confused and uncooperative. This phenomenon has been referred
to as emergence delirium or emergence excitation. Characteristically,
the patient is reacting to the continued presence of the endotracheal
tube, i.e. their gag reex has returned, but they are not yet responding
to verbal commands. Patients in this state can be very difcult to
manage and frequently require additional sedation. Interestingly, they
typically emerge from this additional sedation in a calmer and more
manageable manner. This behavior does not uctuate. The most standard diagnostic instruments are not usable in this situation, which is
generally extremely short lived (Silverstein et al., 2007). Emergence
excitation is probably not a real subset of delirium. It occurs across all
age groups and with rare exceptions is extremely limited in time.
Postoperative delirium (PD) is predominantly a diagnosis of older
patients in that the prevalence becomes signicant after ages 6065.
It has been referred to as interval delirium in that its presentation is
typically 2472 h after the completion of a surgical procedure. Unlike
emergence excitation, postoperative delirium is diagnosed using the
same criteria and instruments used for medical patients. For general
surgery, the incidence of PD is reported from 5 to 15%, ranging up
to 65% for patients with hip fractures (Rudolph and Marcantonio,
2011). The reported incidence in patients undergoing surgery for
hip fracture is higher, ranging from 16 to 62%, with an average rate
of 35% across 12 studies of 1823 patients (Bitsch et al., 2004). Delirium occurs in up to 80% of patients admitted to intensive care. In
this scenario, the age specicity is less marked. The diagnosis of ICU
delirium has required the development of instruments that adjust
to patients who are intubated for mechanical ventilation, but the general criteria are similar (Vasilevskis et al., 2012). Prior to the extensive
description of ICU delirium by Ely et al. (2001), this phenomenon was
frequently termed ICU psychosis and was a diagnosis of exclusion.
Delirium is frequently characterized as hyperactive, in which agitation and restlessness are predominant and hypoactive, in which lack
of responsiveness, slow or absent movement and slowed speech are
predominant (Meagher et al., 2012a). Subsequently, a mixed subtype
has been used to describe patients who vacillate between those two
poles. In addition, the presence of some but not all symptoms has
resulted in the discussion of subsyndromal delirium (Meagher et al.,
2012b). The most recent assessment of these motor types found
that 35% manifested hypoactive delirium, 26% had a mixed picture
and 15% showed hyperactive symptoms. In this study, 24% had no
subtype, most of which were cases referred to as subsyndromal
delirium (Meagher et al., 2012a).
J.H. Silverstein, S.G. Deiner / Progress in Neuro-Psychopharmacology & Biological Psychiatry 43 (2013) 108115
Table 2
Overlap in symptoms from denitions of delirium from the ICD and Diagnostic and Statistical Manuals and the Neuropsychiatric Inventory.
Used with permission from Am J Geriatric Psychiatry 19:12, December 2011.
ICD-10 DSM-II DSMII-R DSM IV DSM V NPI
Clouding of consciousness
Impairment of attention
Perceptual disturbance
Disorganized thinking/speech
Disturbance of sleep
Motor activity change
Disorientation
Memory impairment
Impairment of abstract
thinking or comprehension
Emotional disturbance
Rapid onset and uctuating
symptoms
Causative factor
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
111
112
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J.H. Silverstein, S.G. Deiner / Progress in Neuro-Psychopharmacology & Biological Psychiatry 43 (2013) 108115
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J.H. Silverstein, S.G. Deiner / Progress in Neuro-Psychopharmacology & Biological Psychiatry 43 (2013) 108115
has not, for the most part, included patients with signicant cognitive
impairment before surgery. Patients with mild cognitive impairment
may be at risk for POCD (Bekker et al., 2010). At the moment, there
is little convincing evidence that an incidence of postoperative delirium
in an otherwise intact patient is commonly associated with rapidly progressive dementia.
11. Does dementia cause delirium?
Patients with dementia are prone to episodes of delirium as well as
mixed cognitive pictures that include delirium like symptoms (Holtta
et al., 2011). Larger programs, in the sense that they are not focused
on perioperative care, such as the hospital elder life program seek to
address some of the needs of these patients (Chen et al., 2011). Patients
with pre-existing cognitive impairment are at high risk for delirium.
12. Conclusions
As there is some data to suggest that delirium could be prevented,
there is great interest in understanding the relationship between delirium and dementia. We have seen how overlap in the denitions of
the various entities makes it both logical that there is a relationship
and difcult to make clear determinations, particularly in complex
patients. We have noted that surgery and anesthesia are potent stimuli to the development of delirium. We have reviewed the literature
that seems, on balance, to suggest that patients who develop delirium
are at high risk for POCD/LTCI. We have noted that a small cadre of
patients who are poorly categorized appear to have catastrophic
course, but that these patients are rarely in studies. There is relatively
little data at the moment to suggest that POCD is either permanent or
that surgery and anesthesia accelerate the progression of dementia.
There is much work that needs to be done in this area. Unfortunately, there remains controversy regarding the determination of delirium. With the introduction of the DSM V, there is hope that the
denition of delirium will remain stable for a period of time. Consensus regarding instruments for the determination of delirium would be
valuable. For POCD/LTCI there is so much variability in the methods
that limit the ability to make a coherent assessment. One difculty
is that studies tended to include either high quality delirium or cognitive assessment, but not both. There are currently a number of NIA
funded prospective trials that will use both state of the art delirium
assessments and cognitive batteries are being employed, so we
should have additional prospective datasets to review in a few years.
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