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Postoperative Delirium: Risk Assessment, Prevention,
Detection, and Management
Camilla L. Wong, MD FRCPC MHSc
1
, Maia von Maltzahn, MD FRCPC
2
1
Li Ka Shing Knowledge Institute, St. Michael’s Hospital, University of Toronto;
2
Dalhousie University, Halifax, Nova Scotia
Submitted: November 8, 2020. Accepted: January 14, 2021. Published: March 16, 2021. DOI: 1022374/cjgim.v16iSP1.532.
Copyright: Wong and von Maltzahn
License: This open access article is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). http://creativecommons
.org/licenses/by/4.0
ABSTRACT
There is strong evidence to support prevention of postoperative delirium through comprehensive
geriatric assessment and multicomponent nonpharmacologic interventions. Risk assessment
must be accompanied by communication of the risk to the patient, caregivers, and perioperative
interdisciplinary team to engage all in evidence-based prevention interventions. However, once
postoperative delirium has developed, efforts should be focused on prevention of short- and
long-term adverse effects.
RÉSUMÉ
Des données probantes solides appuient la prévention du délire postopératoire en recourant à
une évaluation gériatrique complète et à des interventions non pharmacologiques à plusieurs
composantes. L’évaluation des risques doit s’accompagner d’une communication du risque au
patient, aux soignants et à l’équipe interdisciplinaire périopératoire afin que tous participent aux
interventions de prévention fondées sur des données probantes. Toutefois, une fois que le délire
postopératoire s’est installé, les efforts doivent être axés sur la prévention des effets indésirables
à court et à long terme.
Background
Delirium is an acute disorder of attention, awareness, and
cognition that tends to fluctuate in severity during the course of
a day and is usually triggered by an underlying medical illness,
drugs, or surgery.
1
Postoperative delirium has been defined as
that which occurs within 1 week postprocedure or until discharge
from hospital, whichever occurs first.
2
The incidence of postoperative delirium varies widely, between
5 and 50%, depending on the type of surgery.
3
Postoperative
delirium is linked to adverse outcomes, including increased
lengths of stay, mortality, and institutionalization.
4
It is also
associated with patient and caregiver distress.
5,6
Beyond the
perioperative period, postoperative delirium is associated with
clinically meaningful impairment in functional recovery at up
to 18 months
7
; moreover, symptoms can persist for 6 months
in one-third of patients.
8
The European Society of Anaesthesiology and American
Geriatrics Society offer evidence-based guidelines for postoperative
delirium management, and the Association of Anaesthetists
provide guidelines on the perioperative care of people with
dementia.
3,9,10
The purpose of this review is to explore the
current evidence and rationale for the prevention, detection,
and management of postoperative delirium in older adults in
the inpatient surgical ward setting.
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Why Is It Important to Assess Cognition
Preoperatively?
The most common independent risk factor for delirium is preexisting
cognitive impairment.
4
Preoperative cognitive screening serves to
document baseline cognitive performance so as to anticipate and
better manage postoperative delirium and postoperative cognitive
dysfunction (POCD).
11
The risk of delirium is linearly and strongly
related to preoperative cognitive performance level.
12
Persons who
develop postoperative delirium also have greater long-term cognitive
decline as compared with those who do not develop delirium.
13
Screening for cognitive impairment can be done quickly using tools
validated for preoperative use and associated with increased risk of
postoperative delirium, such as the Mini-Cog.
14,15
The Mini-Cog
test, which is widely available for online use,
16
includes a clock
drawing task to command with the clock face already provided,
and a 3-word recall task (https://mini-cog.com/).
Who Is at Risk for Developing Postoperative
Delirium?
Overall, 30–40% of cases of delirium are considered preventable,
and, thus, knowledge of associated risk factors is important to
identify persons at increased risk for postoperative delirium.
17
Preexisting cognitive impairment is a major risk factor for
postoperative delirium (odds ratio [OR] = 2.7; 95% confidence
interval [CI]: 1.9–3.8).
18
Additional risk factors include increasing
age, auditory and visual impairment, frailty, functional impairment,
polypharmacy, psychotropic use, depression, illness severity, as
well as alcohol and substance misuse.
18,19
Frailty is a decrease in
physiological reserve across multiple organ systems leading to
increased vulnerability to external stressors, such as surgery.
20
Although comprehensive geriatric assessment (CGA) is the gold
standard method for diagnosing frailty, there are numerous
frailty screening tools validated for use in the surgical setting.
21
Functional decline is a new loss of independence in self-care
activities or as deterioration in self-care skills, measured on
an activities of daily living (ADL) scale (e.g., feeding, bathing,
grooming, using the toilet, transferring, and walking) and/or
on an instrumental activities of daily living (IADL) scale (e.g.,
using the telephone, grocery shopping, using transportation,
cooking, housekeeping, taking medications, and handling
finances).
22,23
Illness severity is also associated with increased
risk for postoperative delirium. As such, persons with acute
admissions for injurious falls, hip fracture, active infections,
underlying metabolic derangements including anemia and
renal insufficiency are at risk for postoperative delirium.
19
Furthermore, the type of surgery is relevant, with a greater risk
for postoperative delirium associated with hip fracture and aortic
vascular procedures.
24
On the other hand, caregiver support is
associated with a lower risk for postoperative delirium (OR =
0.69; 95% CI: 0.52–0.91).
18
Validated delirium prediction rules for elective noncardiac
and cardiac surgery can be used to inform risk assessment.
25,26
What Are Optimal Strategies to Prevent
Postoperative Delirium?
Nonpharmacologic Delirium Prevention
The CGA is a multidimensional, interdisciplinary, diagnostic
process to determine the medical, psychological, and functional
capabilities of a frail older person to develop a coordinated and
integrated plan for treatment and follow-up.
27
A systematic
review found that CGA reduces rates of postoperative delirium
(relative risk [RR] = 0.75; 95% CI: 0.60–0.94).
28
Another systematic review found that multicomponent
nonpharmacologic interventions reduce the incidence of delirium
in hospitalized patients (RR = 0.53; 95% CI: 0.41–0.69).
29
A well-
studied risk mitigation model is the Hospital Elder Life Program
(HELP). HELP includes core intervention protocols to target
delirium risk factors and include for daily visits, orientation,
therapeutic activities, sleep enhancement, early mobilization,
vision and hearing adaptation, fluid repletion, and feeding
assistance to reduce delirium (OR = 0.47; 95% CI: 0.37–0.59, 14
studies, 3,605 patients).
30
Strategies to address modifiable risk
factors for delirium include optimizing sleep–wake cycles via
natural light exposure during daytime, promoting safe mobility
in hospital including avoiding physical restraints, mitigation of
sensory impairment with eyeglasses and hearing aids/amplifiers,
avoiding unnecessary psychoactive drugs, limiting alcohol use, and
using interpreters to enhance communication.
17
In the surgical
setting, additional measures include protocols for bowel routine,
early removal of urinary catheters, monitoring for common
postoperative complications, and pain management.
31
While
opioids may precipitate delirium, poorly controlled pain may
also precipitate delirium.
32
Thus, postoperative pain protocols
should use regularly scheduled acetaminophen which has been
shown to reduce total opioid consumption in the postoperative
period.
33
In most HELP studies, the multicomponent interventions
are carried out by trained volunteers and hospital staff. When
these interventions are delivered by family members, the number
needed to treat to prevent 1 case of postoperative delirium was
5.9 (95% CI: 4.2–11.1).
34
Fluid fasting for more than 6 h is an independent risk factor
for postoperative delirium (OR = 10.6; 95% CI: 1.4–78.6).
35
Thus,
when the surgery is elective, patients at higher risk for delirium
should be prioritized for surgery earlier in the day to reduce
unanticipated prolonged preoperative fasting, sleep alteration,
and interruption of medication schedules.
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Cognitive Prehabilitation
The goal of cognitive prehabilitation is to increase cognitive
reserve before surgery such as through preoperative cognitive
exercise. An observational study demonstrated higher cognitive
activity participation was associated with lower incidence of
postoperative delirium.
36
A randomized trial of using electronic,
tablet-based preoperative cognitive exercise targeting memory,
speed, attention, flexibility, and problem-solving functions
showed the intervention lowered delirium risk in patients who
were at least minimally compliant.
37
Pharmacologic Delirium Prevention
While a systematic review of randomized trials showed that
second-generation antipsychotics compared with placebo may
lower the incidence of postoperative delirium (RR = 0.36; 95% CI:
0.26–0.50])
38
, the largest of these trials also showed that second-
generation antipsychotics were associated with a longer duration
and greater severity of symptoms when delirium occurred.
39
Melatonin, a natural hormone produced by the pineal gland,
is involved in sleep–wake cycle regulation. Ramelteon is a selective
type 1 and type 2 melatonin receptor agonist, though not yet
available in Canada. While a metaanalysis found that perioperative
melatonin or ramelteon administration conferred a lower risk
of developing postoperative delirium, the associated evidence
was limited as only three of the six studies were randomized
trials and had conflicting results.
40
Thus, the current evidence
does not support routine use of melatonin or ramelteon for the
prevention of postoperative delirium.
Metaanalyses have demonstrated that haloperidol (RR = 0.94;
95% CI: 0.77–1.16) and ketamine (RR = 0.83; 95% CI: 0.25–2.80)
do not prevent delirium.
38,41
There have also been negative delirium
prevention trials of cholinesterase inhibitors, gabapentin, and
tryptophan in surgical populations.
42–44
Single randomized trials
favoring pharmacotherapy to prevent postoperative delirium
include parecoxib in joint replacement, methylprednisolone
in hip fracture, intravenous acetaminophen in cardiac surgery,
aripiprazole in neurosurgery, and thiamine in gastrointestinal
surgery, but require replication before widespread adoption.
45–49
Thus, the current evidence does not support routine use of
second-generation antipsychotics or haloperidol for the prevention
of postoperative delirium; multicomponent nonpharmacologic
prevention interventions, therefore, remain the optimal strategy
to decrease the risk of postoperative delirium.
Intraoperative Delirium Prevention Strategies
Intraoperative interventions such as anesthesia type, multimodal
pain management, dexmedetomidine, temperature regulation,
transfusion, and hemodynamic targets are beyond the scope of
this review. For the internist and hospitalist, of utmost importance
is the communication of delirium risk to the anesthesiologist to
inform intraoperative risk reduction strategies.
Special Considerations in Hip Fracture Care
Hip fractures are common in older adults and are a marker
of frailty. Consequently, this population is at high risk for
postoperative delirium which may necessitate care processes
tailored to meet the needs of frailty. For hip fracture care in
particular, a systematic review showed there was a reduction in the
incidence of postoperative delirium with early CGA (RR = 0.81;
95% CI: 0.69–0.94).
50
CGA was defined as a multidisciplinary,
multicomponent intervention addressing multiple health domains
to develop a coordinated, person-centered management plan
and care took place either on a geriatrics or orthopedics ward.
Accelerated hip fracture repair surgery, defined as the goal of
surgery within 6 h of diagnosis, in the HIP ATTACK trial showed
a reduction in the secondary outcome of postoperative delirium
(OR = 0.72; 95% CI: 0.58–0.92) with absolute risk reduction in
this outcome of 3% [95% CI: 1–5].
51
Because uncontrolled pain
as well as opioids are associated with delirium, peripheral nerve
blocks can address both factors. A systematic review assessing
preoperative use of fascia iliaca blocks found a significant
reduction in the secondary outcome of postoperative delirium.
52
How Is Postoperative Delirium Detected?
The clinical presentation of delirium is variable. Motoric subtypes
range from hypoactive (lethargic, withdrawn, decreased motor
activity) to hyperactive (restlessness, irritable, agitated, or
combative), or a mix of both forms. Of the three motor subtypes,
the hypoactive form following surgery is associated with worse
prognosis including 6-month mortality, likely due to delay in
symptom recognition.
53,54
Hypoactive delirium may be missed
because the patient is too withdrawn and the symptoms are
misinterpreted as depression or fatigue, recognition requires a
longitudinal perspective with an understanding of shift from
baseline, and clinicians mistakenly believe that hyperactive
symptoms must be present in delirium.
55
Identifying delirium
allows the clinician to address modifiable contributing factors in a
timely manner, counsel and comfort caregivers to understand the
clinical course, inform prognostication, and plan for follow-up.
The reference standard for delirium is the Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
1
Delirium is often underrecognized by clinicians when using only
routine observations, and as such, brief screening tools have
been developed.
56
Validated screening tools with reasonable
psychometric properties include the short form of the Confusion
Assessment Method (CAM) (positive likelihood ratio [LR] = 9.6;
95% CI: 5.8–16.0 and negative LR = 0.16; 95% CI: 0.09–0.29)
and the 4 “A”s Test (4AT) (sensitivity = 87%; 95% CI: 77–93,
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and specificity = 83%; 95% CI: 73–89).
57,58
In Canada, the most
commonly used screening tool is the short form of the CAM
which is based on the presence of four core features of delirium:
acute onset and fluctuating course of symptoms, inattention, and
either disorganized thinking or altered level of consciousness.
59
The CAM requires specific training in rating each of the features,
including formal testing of attention, and must incorporate
history from informants plus review of medical records.
59
The
4AT comprises four items: (i) alertness, (ii) Abbreviated Mental
Test-4, (iii) attention (months backwards test), and (iv) acute
change or fluctuating course. The advantage of the 4AT is that
item scoring also accounts for patients who may not be able to
undergo cognitive testing because of reduced arousal, such as
in hypoactive delirium.
60
How Does Postoperative Delirium Differ from
POCD?
The core features of postoperative delirium are characterized
by acute, fluctuating changes in cognition with inattention and
either disorganized thought processes or changes in mental
status.
1
In contrast, POCD is a research construct defined as “new
cognitive impairment arising after a surgical procedure.”
2,61
The
incidence of POCD following noncardiac surgery is 12–21%.
2,62
Unlike delirium, which can be diagnosed during bedside clinical
assessment, determination of POCD requires presurgical and
postsurgical psychometric testing, and does not require a
subjective or functional complaint.
61,62
As such, postoperative
delirium is a type of perioperative neurocognitive disorder that
is distinct from POCD.
2
What Is the Optimal Management of Postoperative
Delirium?
While delirium is a diagnosis in the DSM-5, it is better
viewed as a set of symptoms that result from predisposing and
precipitating factors. Optimal management of postoperative
delirium thus requires identification of contributing factors
followed by management of treatable precipitants. Potentially
modifiable precipitants may include medications, withdrawal
from held medications or other substances, infection, electrolyte
abnormalities, or other complications such as myocardial
infarction or venous thrombosis. The evaluation should at a
minimum include a history (substance use, medication list
and changes), physical examination looking for common
postoperative complications (vital signs, urinary retention,
constipation, volume status, surgical incision site, asymmetric
leg swelling), and investigations focused on the postoperative
setting (electrolytes, complete blood count, glucose, troponin,
calcium, ECG; and infectious work-up like chest x-ray, blood
cultures, procedure-specific infection imaging, urine analysis).
Brain imaging is not a routine part of the evaluation and its use
should be informed based on clinical judgment.
19,31
Careful medication review for culprit medications should
be linked with the goal of tapering, discontinuing, and/or
substituting with alternatives when possible. Increased delirium
risk is associated with sedative-hypnotics such as benzodiazepines
(OR 3.0, 95% CI 1.3–6.8), anticholinergic medications such as
antihistamines (OR 1.8, 95% CI 0.7–4.5), meperidine (OR 2.7,
95% CI 1.3–5.5), and dihydropyridines in cardiac surgery (OR
2.4, 95% CI 1.0–5.8).
32,63
Benzodiazepines are associated with
longer duration of a first episode of delirium.
64
There are three Cochrane systematic reviews of different
drug classes in the treatment of delirium. Antipsychotics do
not reduce delirium severity (SMD −1.08, 95% CI: −2.55–0.39)
and do not resolve symptoms (RR = 0.95; 95% CI: 0.30–2.98)
when compared to placebo.
65
There is insufficient evidence to
determine whether benzodiazepines are effective.
66
There is no
difference in delirium duration to support the use of cholinesterase
inhibitors.
67
Thus, because of the low risk of adverse events,
reinforcement of the nonpharmacological methods used for
delirium prevention is recommended as a first step in delirium
management. Family members can serve as a reorienting and
reassuring stimulus and may reduce the duration of delirium.
31,68
In the scenario where there are refractory distressing
psychotic symptoms (such as hallucinations or delusions) or the
symptoms of delirium imminently threaten the administration or
maintenance of life-sustaining medical care (such as mechanical
ventilation or dialysis catheters), expert opinion suggests the
use of antipsychotics at the lowest effective dose for the shortest
possible duration.
17
At care transitions, documentation of delirium should be
in the discharge summary communication to the primary care
provider to screen for cognitive deficits postdischarge.
11
Summary
In summary, there is strong evidence to support prevention through
CGA and multicomponent nonpharmacologic interventions.
Risk assessment must be accompanied by communication of the
risk to the patient, caregivers, and perioperative interdisciplinary
team to engage all in evidence-based prevention interventions.
However, once postoperative delirium has developed, aside
from addressing precipitating causes, there are limited drug
management strategies. Because postoperative delirium is
associated with short- and long-term adverse effects, efforts
should be focused on prevention.
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Perioperative Medicine Special Issue
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