Download Postoperative delirium (POD)

28 February 2014
No.07
POSTOPERATIVE DELIRIUM
’’Grannies gone wild”
ZN Moyce
Moderator: Kim de Vasconcellos
School of Clinical Medicine
Discipline of Anaesthesiology and Critical Care
CONTENTS
INTRODUCTION ................................................................................................... 3
DEFINITION .......................................................................................................... 3
CLASSIFICATION ................................................................................................ 5
INCIDENCE .......................................................................................................... 5
PATHOPHYSIOLOGY .......................................................................................... 5
RISK FACTORS ................................................................................................... 6
DIAGNOSIS .......................................................................................................... 8
OUTCOME/SEQUELAE ..................................................................................... 11
PREVENTION ..................................................................................................... 11
META-ANALYSIS FINDINGS ............................................................................. 12
TREATMENT ...................................................................................................... 18
RECOMMENDATIONS ....................................................................................... 19
WHAT’S ON THE HORIZON .............................................................................. 19
CONCLUSION .................................................................................................... 20
REFERENCES.................................................................................................... 21
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POSTOPERATIVE DELIRIUM ’’GRANNIES GONE WILD”
INTRODUCTION
As the global population ages, so the number of elderly patients with more comorbidities requiring surgical interventions and procedures is increasing[1-3] These
patients represent a significant proportion of the estimated annual 200 million
surgeries conducted globally[4]. Cognitive decline is one of the common causes of
functional impairment worldwide and central nervous system dysfunction is a
recognised complication that can occur following both cardiac and non-cardiac
surgery[1,3]. The word ‘delirium’ is derived from the Latin term meaning “off the
track” and was described by Hippocrates more than 2500 years ago[5].
Postoperative delirium (POD) is one of the most frequently encountered
perioperative complications. It is an acute impairment of cognition and or
perception, which can be diagnosed at the bedside with specific diagnostic tools.
It is a complex disease and often multifactorial, therefore POD continues to be
underdiagnosed and poorly managed[6]. POD has a classic fluctuating course,
most commonly days 1 to 3 postoperatively with symptoms worse at night [7, 8]. If
not systematically tested for POD can be easily overlooked and early diagnosis
and resolution is likely to produce the most favorable outcomes [7, 9].
DEFINITION
There are two standard definitions used for delirium (DSM IV-TR/ DSM V) : an
acute and fluctuating disturbance of consciousness with signs of inattention,
accompanied by a change in cognition and perception (Table 1) [10, 11]; or (ICD 10)
an aetiologically non-specific organic cerebral syndrome characterized by
concurrent disturbances of consciousness and attention, perception, thinking and
memory, including disturbances of emotion, psychomotor and the sleep–wake
cycle (Table 2) [12].
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Table 1: Diagnostic criteria of the DSM-V for postoperative delirium[11]
The Diagnostic and Statistical Manual of Mental Disorders, Fifth
Edition (DSM-V) diagnostic criteria for delirium
A: Disturbance in attention (ie, reduced ability to direct, focus, sustain,
and shift attention) and awareness.
B: Change in cognition (eg, memory deficit, disorientation, language
disturbance, perceptual disturbance) that is not better accounted
for by a preexisting, established, or evolving dementia.
C: The disturbance develops over a short period (usually hours to
days) and tends to fluctuate during the course of the day.
D: There is evidence from the history, physical examination, or
laboratory findings that the disturbance is caused by a direct
physiologic consequence of a general medical condition, an
intoxicating substance, medication use, or more than one cause
Table 2: ICD-10 definition for postoperative delirium[12]
ICD-10 definition of postoperative delirium
An aetiologically non-specific organic cerebral syndrome
characterized by concurrent disturbances of consciousness and
attention, perception, thinking, memory, psychomotor behavior,
emotion and the sleep-wake schedule. The duration is variable and
the degree of severity ranges from mild to very severe
Includes: Brain syndrome, Confusional state (non-alcoholic),
Infective psychosis, Organic reaction, Psycho-organic syndrome
Excludes: Delirium tremens, alcohol induced or unspecified
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CLASSIFICATION [1,5-7,13-19]
Delirium can be classified into three subtypes:
Hyperactive: most frequently recognized form as it is characterized by agitation,
aggression acute disorientation, restlessness, hallucinations and emotional
liability. It has been associated with increased use of benzodiazepines, oversedation and physical restraints.
Hypoactive: occurs more commonly, but is often unrecognized as the patient
usually presents with a flat affect and is withdrawn, lethargic, and quiet, but
disoriented and confused. This is however associated with prolonged
hospitalization and secondary complications.
Mixed: a combination of hyperactive and hypoactive types in which the patient’s
behaviors fluctuate from agitated to calm moods commonly associated with
daytime sedation and nighttime agitation.
Sub-syndromal delirium: patient displays one or more symptoms of delirium but
do not meet the defined criteria
INCIDENCE
There is a wide variation in the reported incidence of delirium ranging from 0-73%
depending on patient population and the type of surgery [6, 8, 9]. The incidence of
POD following major orthopaedic surgery can range from 16-62% [8]. The
incidence is higher in patients with terminal illnesses like cancer or AIDS/HIV
related illness and extensive surgical stress [6, 8].
PATHOPHYSIOLOGY[1, 3, 5, 13, 16-18]
The pathophysiological mechanisms of POD are not fully understood, however it
is probably multifactorial and includes some or all of the various hypotheses given
below.
Neurotransmittor theory: decrease in oxidative metabolism of the brain causes a
decrease in neurotransmittors which causes neuronal dysfunction.
Neurotransmittors implicated are acetylcholine, dopamine, gamma-aminobutyric
acid (GABA), tryptophan, melatonin and serotonin. Increased levels of dopamine
and decreased production of acetylcholine can lead to neuronal excitability which
can precipitate delirium.
Medication theory: perioperative drugs and associated neurotoxicity. Age related
changes to the blood brain barrier (BBB) could affect the permeability of the BBB
and alter the entry of drugs into the CNS.
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Surgical theory: inflammation from both anesthetics and surgical interventions as
the aetiology of neuronal changes. Stress responses, release of inflammatory
cytokines, increased circulation of cortisol, and sleep deprivation are believed to
cause changes in neuronal pathways triggering delirium.
Impaired anti-inflammatory feedback of the aged brain can cause exaggerated or
prolonged production of cytokines.In animal studies they found increased
expression of interleukin 1β was associated with cognitive decline. The
inflammatory process can also lead to a prothrombotic state which can lead to
decreased cerebral blood flow.
Patient theory: factors such as frailty and any preoperative cognitive deficits.
Environmental theory: disorientation and unfamiliar surroundings as the
contributory factor in POD
RISK FACTORS
Although the mechanism of POD is not completely understood, there are
significant details in literature describing associated perioperative risk factors. A
list of the most common conditions/stressors is given below. Specific attention
should be paid to identifying and correcting these risk factors if possible (Table 36) [6,7 9,13].
Table 3: A list of preoperative risk factors for postoperative delirium [6, 7, 9, 13]
Demographic related:
 Age >70 years
 Male sex
 Low education level
 Malnutrition
 Alcohol and drug use
Comorbidities related:
 Preoperative cognitive and physical
status
 Renal or hepatic disease
 HPT, DM, PVD, CCF, OSA, CVA
 Hb <10
 Smoking, COPD
 Low albumin
 Abnormal electrolytes, glucose
 Hearing or visually impaired
Surgery related:
Anaesthetic related:
 Aortic aneurysm, cardiac,
 Fasting time > 6hrs
thoracic, abdominal,
 Use of premedication:
cataract and hip
benzodiazepines
replacement surgery
 Use of anticholinergic agents
 ASA III –IV
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Table 4: A list of intraoperative risk factors for postoperative delirium [6 7,9,13]
Surgery related:
Anaesthetic related:
 Prolonged surgery
 Hypotension
 Blood loss >1L
 Hypoxia, hypocarbia,
hypercarbia
 Hypothermia
 Use of ketamine,
benzodiazepines,
propofol
 Long acting opioids
 Embolism
Table 5: A list of postoperative risk factors for postoperative delirium
 Pain
 Sepsis
 Hypotension requiring vasopressors
 Hypoxia requiring ventilation
 Electrolyte or metabolic abnormalities
 Sensory deprivation or overload
 Sleep deprivation
 Anxiety
 Restraints and catheters
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[6, 7, 9, 13]
Table 6: A list of drugs associated with postoperative delirium[5]
Memory aid for delirium precipitants – think DELIRIUM
Drugs (withdrawal/toxicity, anticholinergics)/Dehydration
Electrolyte imbalance
Level of pain
Infection/Inflammation (post surgery)
Respiratory failure (hypoxia, hypercapnia)
Impaction of faeces
Urinary retention
Metabolic disorder (liver/renal failure, hypoglycaemia) Myocardial infarction
DIAGNOSIS
To assess the patient’s degree of cognitive impairment, it is vital to have
established a baseline for comparison. Therefore, a good preoperative evaluation
should include a formal cognitive assessment in patients at risk of developing
delirium. DSM IV and ICD 10 are the gold standards but they require expertise
and are time consuming[5, 7]. Delirium may be identified with the help of delirium
assessment tools like the mini mental state exam (MMSE) (Table 7), the
Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and
Intensive Care Delirium Screening Checklist (ICDSC)[5, 7, 13].
The MMSE is one of the most widely used tools to test cognition. Although it was
not specifically designed for delirium it can be used to assess changes in cognitive
function. It is therefore essential to do baseline MMSE testing with repeat testing
to assess for changes. A drop of > 2 points from baseline is suggestive of
delirium[6, 15]. CAM-ICU is the most commonly used tool. It has high sensitivity and
specificity, a rapid assessment tool <5 minutes and its easy to use.
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When used in ICU it is utilized in conjunction with the Richmond Agitation and
Sedation score (RASS) and should be performed daily on patients at risk of POD
(Figure 1) [6,7,9,13,15]
Table 7: Criteria of the mini mental state exam[17]
Points
Orientation
Name: season/date/day/month/year
5 (1 for each)
Name: hospital/floor/town/province/country
5 (1 for each)
Registration
Identify 3 objects by name and ask patient to repeat it
3 (1 for each)
Attention and calculation
Serial 7s (subtract from 100-5 subtractions)
5 (1 for each)
Recall
Recall the 3 objects presented earlier
3 (1 for each)
Language
Name pencil and watch
2 (1 for each)
Repeat “No ifs, ands or buts”
1
Follow 3 step command (take this paper, fold it in half and
place it on the table)
3 (1 for each)
Write “close your eyes” and ask patient to obey written
command
1
Ask patient to write a sentence
1
Ask patient to copy a design (intersecting pentagons)
1
TOTAL
30
Memory aid mnemonic for CAM - think CA2MS:
Delirium diagnosis requires CA2 and either M or S
Changeable course
Acute onset + Attention poor
Muddled thinking
Shifting consciousness
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Figure 1: Chart for the stepwise approach to diagnosing delirium[13]
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OUTCOME/SEQUELAE
Postoperative delirium (POD) is associated with serious postoperative
complications, which decrease functional capacity, prolong recovery and
discharge, and directly increase healthcare costs. Patients suffering delirium have
increased numbers of surgical complications, including fractures (due to falls),
urinary and respiratory tract infections, and vascular events.
Delirium also increases long-term morbidity through delayed functional and
cognitive recovery, subsequent institutionalisation and postoperative depression [3,
5, 9, 13, 15, 16]
Radtke et al found that delirium was associated with a higher incidence
of postoperative cognitive dysfunction at 7 days and 3 months postoperative [20].
PREVENTION
Due to the multifactorial nature of POD the approach to prevention of POD needs
to be multi-interventional.
Preoperative prevention [6, 7, 17, 21]
 Detailed preoperative history
 Detailed drug history
 Detection of any sensory or perceptual deficits
Identifying patients at risk is essential and a comprehensive preoperative
assessment is vital to provide possible causes that could increase the risk of
POD. It’s important to note any pre-operative cognitive impairments and a patient
with pre-exising sensory or perceptual deficits is likely to have an increased
chance of POD developing.
By identifying these high risk patients we should then ensure that all intraoperative
and postoperative strategies are adhered to. Preoperative prediction scores assist
in identifying these high risk patients but can’t be used to exclude the possiblilty
of delirium developing postoperatively (Table 8) [17, 21].
Table 8: Preoperative prediction scores for delirium for both cardiac and noncardiac surgery
Intraoperative prevention [6, 9, 17, 19, 21]:
 Ensure adequate oxygenation and perfusion
 Correct any electrolyte imbalances
 Adjust drug doses accordingly
 Avoid anticholinergic agents
Postoperative prevention [6, 7, 13, 21]:
 Provide visual and hearing aids when appropriate
 Early mobilisation
 Orientation
 Family visits
 Sleep hygiene
 Adequate pain management
 Aviod volume depletion and electrolyte abnormalities
 In ICU: sedation hold
 Daily delirium monitoring
META-ANALYSIS FINDINGS [22]
Despite advances in both perioperative care and surgical interventions, geriatric
patients still experience POD. POD is associated with an increase in both
morbidity and mortality and had a direct burden on health care costs and
resources[1,8,14,23].
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Outcomes of POD could be improved by systematic identification of important risk
factors for delirium and identification of preventative measures that decrease the
incidence of delirium and the subsequent associated morbidity [24]. It is still not
clear which are the most effective interventions to decrease POD so we planned
to look at perioperative interventions to decrease delirium in noncardiac surgery.
The purpose of our systematic review and meta-analysis was to determine
the efficacy of both pharmacological and non-pharmacological perioperative
interventions to decrease delirium.
Method
We posed the following research question: ‘Which peri-operative interventions
during non-cardiac surgery have been independently associated with a reduction
in delirium within the first seven postoperative days?’ Trials were considered
eligible if they tested a peri-operative intervention aimed at reducing delirium after
non-cardiac surgery in a randomised controlled manner.
The primary outcome was the incidence of delirium within seven days of surgery.
An electronic search of four databases was conducted. The Preferred Reporting
Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were
adhered to[25]. We included randomised controlled trials of non-cardiac surgery
with a peri-operative intervention and that reported postoperative delirium, and
identified 29 trials.
A manual search of the reference lists of all included papers was also conducted
for further eligible studies. Concordance of article extraction was determined using
a kappa statistic.Using a standardised data extraction sheet, we extracted data
on: the outcome of delirium following a peri-operative intervention; the specific
intervention tested; patient age; type of surgery; and the use of premedication.
The quality of each study was assessed using the Jadad score[26] Meta-analysis
was conducted using Review Manager Version 5.1 (The Nordic Cochrane Centre,
The Cochrane Collaboration, Copenhagen, Denmark, 2011). Heterogeneity
between studies was assessed using univariate chi-squared analysis. Random or
fixed effects models were used based on the presence or absence of significant
heterogeneity between studies, respectively. Pooled dichotomous outcomes were
reported as odds ratios (OR) with 95% CI.
Where an intervention was associated with benefit, a funnel plot was constructed
to determine if the outcomes reported were affected by publication bias. For
interventions that were not significantly associated with a decrease in delirium, a
power analysis was conducted to determine if the sample size was adequately
powered for the outcome. The power analysis was based on the incidence in the
control group, with an expected 25% relative risk reduction for an efficacious
intervention.
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Results
We identified 1376 studies from our literature search, of which 56 studies were
selected for full paper analysis; the kappa statistic was 83%. From these studies,
29 were finally included in our meta-analysis (Fig.1). Nineteen of the studies were
of a high quality with a Jadad score of 4 or 5 [16– 34], and 10 were low-quality
studies with a Jadad score < 4.
The following interventions to decrease delirium were tested in more than one trial
and a meta-analysis was therefore possible: geriatric (or multicomponent)
consultation vs standard care, where peri-operative geriatric consultation
constituted a proactive, comprehensive geriatric assessment along with
management and rehabilitation to decrease the outcome of delirium[27-29]; deep vs
light anaesthesia[30-32]; intravenous vs inhalational anaesthesia [33, 34]; general vs
regional anaesthesia[35-37]; haloperidol vs placebo[38-40]; donepezil (a
cholinesterase inhibitor) vs placebo[41-43]; gabapentin vs placebo [44, 45]; and bright
light therapy vs standard care [46, 47].
Bright light therapy was instituted after extubation of the trachea and study
patients received two hours of bright light therapy daily. Only two interventions
were associated with significantly decreased delirium: peri-operative geriatric
consultation and light as opposed to deep anaesthesia. There was no significant
heterogeneity for these two interventions.
Figure 2: Flow chart of identification of randomized controlled trials included in the meta-analysis.
Potentially relevant
studies identified by
electronic database
search and manual
searching (n=1376)
Potential
studies
retrieved for
more detailed
evaluation
(n=56)
Selected trials
included in
meta-analysis
(n=29)
Letter, editorial, review
(n=178)
Cardiac (n=375)
Non-human (n=1)
Non-adult (n=65)
No delirium
outcome/intervention
(n=649)
Foreign language (n=52)
Duplicates (n=3)
No surgical control
group/ not RCT (n=6)
Same cohort (n=4)
Abstract/unable to
obtain specific data
(n=9)
Protocol/ meta-analysis
(n=5)
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Figure 3: Meta-analysis of the efficacy of peri-operative geriatric consultation vs standard care on
outcome of postoperative delirium. M-H, Mantel-Haenszel
Figure 4: Meta-analysis of the efficacy of depth of anaesthesia vs standard care on outcome of
postoperative delirium. M-H, Mantel-Haenszel.
For the other interventions, the point estimate suggested possible protection with
the use of prophylactic haloperidol, bright light therapy and general as opposed to
regional anaesthesia. The power analyses showed that the sample size was
inadequate for all the interventions included in the meta-analysis, with the
exception of the peri-operative geriatric consultation.
Discussion
The main findings of this meta-analysis are that perioperative geriatric
consultations, which included multicomponent interventions, and lighter as
opposed to deeper anaesthesia were effective in decreasing postoperative
delirium. The point estimate for perioperative geriatric consultation was robust
without heterogeneity, yet these clinical trials are at a high risk of bias due to
inadequate randomisation and/or blinding.
The point estimate for deep vs light anaesthesia showed significant heterogeneity,
and there may be publication bias associated with this intervention. Delirium is a
common complication following hip fracture surgery and the three trials of perioperative geriatric consultations were conducted in this population.
Page 15 of 24
Multi-component and systemic assessment addressed urinary tract infections,
hypoxia, anaemia, constipation, sleep disorders and nutritional deficiencies, which
may all have a role in the aetiology and duration of delirium[28]. This meta-analysis
lends support to multidisciplinary peri-operative medicine interventions to
decrease delirium. Delirium is multifactorial, and anaesthetic technique is another
potentially modifiable risk factor. Intra-operative monitoring of depth of
anaesthesia using bispectral index (BIS) or auditory evoked potentials has shown
to facilitate titration of anaesthetic drugs. Bispectral index values between 40 and
60 during anaesthesia have been associated with decreased awareness, earlier
recovery profiles and faster emergence[30].
Chan et al. demonstrated that titrating anaesthetic agents to maintain BIS
between 40 and 60 and avoiding episodes of deep anaesthesia (BIS < 40)
reduced the risk of delirium (p = 0.01)[30]. Sieber et al. found that light sedation
(BIS > 80) during spinal anaesthesia for orthopaedic surgery decreased the
occurrence of delirium by 50% when compared with deep sedation (BIS ~ 50) (p =
0.02)[48].
Depth of anaesthesia guided by auditory evoked potentials
demonstrated that patients with lighter anaesthesia sustained fewer intraoperative events, had higher blood pressure, required less fluids or vasopressors,
and were at a lower risk of developing early postoperative decline [31].
Regarding the intra-operative measures that were identified, neither intravenous
vs inhalational anaesthesia, nor regional vs general anaesthesia, showed any
effect on postoperative delirium. Although both of these analyses were
underpowered, the point estimates favoured inhalational and general anaesthesia.
In contrast, another meta-analysis of the efficacy of general and regional
anaesthesia failed to show a significant difference (five studies), and suggested
that general anaesthesia may increase the risk of developing postoperative
cognitive dysfunction [49].
Our meta-analysis has found a trend to protection with the use of haloperidol. The
dose of haloperidol varied between the studies. Wang et al. used 0.5 mg
haloperidol as an intravenous bolus postoperatively, followed by an infusion at 0.1
mg.hr for 12 h; Kaneko et al. administered 5 mg haloperidol intravenously per day
for five days, and Kalisvaart et al. used oral haloperidol 1.5 mg pre-operatively
and for three days postoperatively[38-40]. A recent meta-analysis conducted by
Teslyar et al. looked at antipsychotics as a group (haloperidol, olanzapine and
risperidone) and they also showed a trend to a reduction in delirium with the perioperative use of antipsychotics[50]
LImitations
There are a number of limitations to this meta-analysis. Firstly, of all the possible
interventions investigated to decrease delirium, only peri-operative geriatric
consultation and light vs deep anaesthesia were adequately powered. It is
therefore possible that certain of the other interventions are efficacious; however,
further research would be required to confirm this.
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Secondly, peri-operative geriatric consultation consultation studies were limited to
orthopaedic surgery. This research needs to be extended to other non-cardiac
surgeries.Furthermore, the nature of multi-component consultations makes it
difficult to exclude a strong bias due to poor randomisation and blinding, which is
evident in this meta-analysis. In the pharmacological intervention studies, there
was no standardisation of the anaesthetic technique. This is an important
limitation, as this meta-analysis suggested that depth of anaesthesia may be an
important determinant of delirium.Furthermore, there was no standardisation of
the dosage of the pharmacological intervention between the trials analysed and
this may be an important confounder in some studies.
We also excluded foreign language studies, which could have impacted on the
results of the meta-analysis. Finally, few studies assessed pre-operative risk for
delirium, with no standardization in timing of postoperative testing either. A
standardised protocol for pre-operative risk assessment and outcome
determination would be desirable in future studies. In conclusion, the main
findings of this meta-analysis are that peri-operative geriatric consultations that
involve multi-component interventions, and lighter anaesthesia, are potentially
effective in decreasing the outcome of delirium.
Zhang et al did a systematic review and meta-analysis of randomised controlled
trials of strategies to prevent POD. Their review entailed randomised controlled
trials for both cardiac and noncardiac surgery[51]. They found that
dexmedetomidine sedation; multicomponent interventions and antipsychotics are
useful in preventing postoperative delirium[51]. Dexmedetomidine sedation was
used postoperatively in cardiac surgery therefore was not included in our analysis.
Both studies found huge heterogeneity of the interventions among the trials and
that multicomponent (geriatric) interventions were potentially effective in
decreasing the outcome of POD [22, 51]
Our study only included RCT, which looked at haloperidol in decreasing the
outcome, which only indicated a trend to protection whereas Zhang et al found
protection with antipsychotics looking at both typical and atypical antipsychotics [22,
51]
.Our point estimates favoured inhalational anaesthesia compared to intravenous
and general anaesthesia compared to regional anaesthesia [22]. Zhang et al found
that type of anaesthesia had no effect on the outcome of delirium[51].
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TREATMENT
Due to the multifactorial nature of POD, a multicomponent strategy needs to be
implemented for adequate treatment. Once the diagnosis of delirium is made, it is
vital to exclude any identifiable causes and treat appropriately
Non-pharmacological [5-7, 9, 15, 16, 18, 19, 21]
Need to optimise the preventive measures
 orientation
 sleep hygiene
 early mobilisation
 vision and hearing devices
 adequate pain management
 remove any lines or catheters
 do not use unnecessary physical restraints
 stop any deliriogenic drugs
Pharmacological
Antipsychotics:
Haloperidol is a dopamine receptor antagonist and acts centrally to decrease
hallucinations and delirium[18]. Side effects include prolonged QT, extrapyramidal
side effects and neuroleptic malignant syndrome. Although the evidence is
inconclusive, current recommendation is haloperidol as the agent of choice for the
treatment of delirium[5, 7, 15]
Studies have shown a decrease in the incidence of POD and a reduction in the
severity POD with the use of haloperidol. The dose of haloperidol is determined by
route of administration, the age of the patient and the severity of the agitation[5].
High doses of >4.5mg per day are associated with increases in the incidence of
adverse effects[6]
Haloperidol dosage[15]:
ICU: haloperidol 1-2mgIVI repeated every 20min until resolution of agitation.
Taper dose over several days.
Ward: haloperidol 1mg po/IM/IV stat ; maintenance 0.25-0.5mg 4 hrly. Taper over
several days
Atypical antipsychotics eg olanzapine/ risperidone are alternative agents. They
have however not been shown to be superior to haploperidol in the treatment of
delirium[15].
Benzodiazepines
The use of benzodiazepines is discouraged perioperatively in patients at risk of
delirium. They have a dose dependent association with the incidence of POD.
They however have a role in POD associated with withdrawal syndrome due to
chronic alcohol or sedative use[5-7, 15]
Page 18 of 24
Alpha-2 agonists
Perioperative use of dexmedetomidine has been shown to reduce the prevalence
of POD in ICU. Zhang et al found that although the studies used in the metaanalysis were poor quality and had inconsistent definitions it still supported the
effectiveness of dexmedetomidine sedation in preventing delirium in ICU[51].
Opioids
Opioids have an important role in palliation of terminal illnesses where severe pain
might be the aggravating factor for the delirium[5]
RECOMMENDATIONS
Due to the multifactorial nature of delirium, we are most likely to realise benefit
when multiple interventions are instituted. Our meta-analysis supports this
approach where peri-operative geriatric consultations have been shown to be a
potentially very powerful intervention to decrease delirium. We recommend that
future interventional trials for delirium should consider a multi-component
approach to preventing delirium.
WHAT’S ON THE HORIZON
Serum biomarkers generated by the various pathological processes of delirium
may be helpful in identifying patients at risk of delirium, diagnosing delrium and
assessing the severity of delirium[52-54]. Inflammatory biomarkers interleukin
1,2,6,8, natural killer cell activity and C-reactive protein (CRP) have been
implicated in being predictive markers of delirium[52-56]. Zhang et al found that a
change in the CRP from admission to ICU was associated with an increased risk
of developing delirium[54].
S100 calcium binding protein B (S100 β) which is a protein present in astrocytes
and oligodendrocytes, indicates blood brain barrier disruption and has been
implicated in the duration of delirium[53]. Fast track surgery has also been
associated with a reduction in the incidence of POD. Krenk et al found that in
elderly patients, fast track orthopaedic surgery with multimodal opioid-sparing
analgesia will decrease the incidence of delirium[57]. So specific identification of
biomarkers in patients at risk and multimodal optimisation of perioperative care
may be effective in identifying patients at risk and improving the outcome of POD.
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CONCLUSION
Currently research regarding geriatric anaesthesia and postoperative cognitive
complications is on the rise. POD is a common complication seen in our geriatric
population that has implications on both morbidity and mortality. Early diagnosis
and prompt implentation of pharmacological and non-pharmacological
interventions to prevent or minimise POD is required to decrease these adverse
outcomes.
Page 20 of 24
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
Bekker, A.Y. and E.J. Weeks, Cognitive function after anaesthesia in the elderly. Best
Pract Res Clin Anaesthesiol, 2003. 17(2): p. 259-72.
Robinson, T.N.R., C. D.; Tran, Z. V.; Brenner, L. A.; Moss, M., Motor subtypes of
postoperative delirium in older adults. Archives of Surgery, 2011. 146(3): p. 295-300.
Terrando, N., et al., Perioperative cognitive decline in the aging population. Mayo Clin
Proc, 2011. 86(9): p. 885-93.
Weiser, T.G., et al., An estimation of the global volume of surgery: a modelling strategy
based on available data. Lancet, 2008. 372(9633): p. 139-44.
A. Rudra, S.C., J. Kirtania, S. Sengupta, G. Moitra, S. Sirohia, R. Wankhade, S. Banerjee,
Postoperative delirium. Indian J Crit Care Med Oct-Dec 2006 2006. 10(4): p. 235-240.
Wass, S., P.J. Webster, and B.R. Nair, Delirium in the elderly: a review. Oman Med J,
2008. 23(3): p. 150-7.
Bilotta, F., et al., Postoperative delirium: risk factors, diagnosis and perioperative care.
Minerva Anestesiol, 2013. 79(9): p. 1066-76.
Deiner, S. and J.H. Silverstein, Postoperative delirium and cognitive dysfunction. Br J
Anaesth, 2009. 103 Suppl 1: p. i41-46.
Brooks, P.B., Postoperative delirium in elderly patients. Am J Nurs, 2012. 112(9): p. 38-49;
quiz 51, 50.
American Psychiatric Association. Diagnostic and statistic manual of mental
disorders. revised, DSM-IV-TR. 4th ed. Washington, DC: . 2000.
Association, A.P., Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 5th
ed. Washington, DC: American Psychiatric Association. 2013.
World Health Organisation. The international classification of diseases, 10th
revision: ICD-10. In: Mental and behavioral disorders (F00-F99). Geneva: World
Health Organisation. 1992.
Flynn Makic, M.B., Preventing delirium in postoperative patients. J Perianesth Nurs, 2013.
28(6): p. 404-8.
Rudolph, J.L., et al., Delirium is associated with early postoperative cognitive dysfunction.
Anaesthesia, 2008. 63(9): p. 941-7.
Robinson, T.N. and B. Eiseman, Postoperative delirium in the elderly: diagnosis and
management. Clin Interv Aging, 2008. 3(2): p. 351-5.
Strom, C., L.S. Rasmussen, and F.E. Sieber, Should general anaesthesia be avoided in
the elderly? Anaesthesia, 2014. 69 Suppl 1: p. 35-44.
Parikh, S.S. and F. Chung, Postoperative delirium in the elderly. Anesth Analg, 1995.
80(6): p. 1223-32.
Dr David Connor, R., Anaesthesia and C. Dr William English, Intensive Care Medicine,
DELIRIUM IN CRITICAL CARE
AESTHESIA TUTORIAL OF THE WEEK 232. 18TH JULY 2011.
Gregory L. Fricchione, M.D., et al., Postoperative Delirium. Am J Psychiatry 2008. 165(7):
p. 803-812.
Radtke, F.M., et al., Monitoring depth of anaesthesia in a randomized trial decreases the
rate of postoperative delirium but not postoperative cognitive dysfunction. Br J Anaesth,
2013. 110 Suppl 1: p. i98-105.
Postoperative Management: general principles, in The Medicine Consult Handbook. 2011.
Moyce, Z., R.N. Rodseth, and B.M. Biccard, The efficacy of peri-operative interventions to
decrease postoperative delirium in non-cardiac surgery: a systematic review and metaanalysis. Anaesthesia, 2014.
Bilotta, F.D., A.; Stazi, E.; Titi, L.; Zeppa, I. O.; Cianchi, A.; Rosa, G.; Paoloni, F. P.;
Bergese, S.; Asouhidou, I.; Ioannou, P.; Abramowicz, A. E.; Spinelli, A.; Delphin, E.;
Ayrian, E.; Zelman, V.; Lumb, P., Early postoperative cognitive dysfunction and
postoperative delirium after anaesthesia with various hypnotics: study protocol for a
randomised controlled trial--the PINOCCHIO trial. Trials, 2011. 12: p. 170.
Page 21 of 24
24. Patti, R., et al., Risk factors for postoperative delirium after colorectal surgery for
carcinoma. Eur J Oncol Nurs, 2011. 15(5): p. 519-23.
25. Moher, D., et al., Preferred reporting items for systematic reviews and meta-analyses: the
PRISMA statement. BMJ, 2009. 339: p. b2535.
26. Jadad, A.R., et al., Assessing the quality of reports of randomized clinical trials: is blinding
necessary? Control Clin Trials, 1996. 17(1): p. 1-12.
27. Deschodt, M.B., T.; Flamaing, J.; Detroyer, E.; Broos, P.; Haentjens, P.; Boonen, S.;
Milisen, K., Preventing delirium in older adults with recent hip fracture through
multidisciplinary geriatric consultation. Journal of the American Geriatrics Society, 2012.
60(4): p. 733-9.
28. Lundström, M.O., B.; Stenvall, M.; Karlsson, S.; Nyberg, L.; Englund, U.; Borssén, B.;
Svensson, O.; Gustafson, Y. Postoperative delirium in old patients with femoral neck
fracture: a randomized intervention study. Aging clinical and experimental research, 2007.
178-86.
29. Marcantonio, E.R.F., J. M.; Wright, R. J.; Resnick, N. M. Reducing delirium after hip
fracture: a randomized trial. Journal of the American Geriatrics Society, 2001. 516-22.
30. Chan, M.T.V.C., B.; Gin, T.; Lee, T.; Koo, E. Cognitive dysfunction after anesthesia: a
randomized controlled trial. Journal of Neurosurgical Anesthesiology, 2010. 408-9.
31. Jildenstål, P.K.H., J. L.; Rawal, N.; Gupta, A.; Berggren, L. Effect of auditory evoked
potential-guided anaesthesia on consumption of anaesthetics and early postoperative
cognitive dysfunction: a randomised controlled trial. European journal of anaesthesiology,
2011. 213-9.
32. Sieber, F.E.Z., K. J.; Gottschalk, A.; Blute, M. R.; Lee, H. B.; Rosenberg, P. B.; Mears, S.
C. Sedation depth during spinal anesthesia and the development of postoperative delirium
in elderly patients undergoing hip fracture repair. Mayo Clinic proceedings. Mayo Clinic,
2010. 18-26.
33. Cai, Y.H., H.; Xue, R.; Liu, P.; Feng, G.; Dong, W.; Yu, B.; Zhao, M. Cognitive function
correlations with apolipoprotein E 4 single nucleotide polymorphism in 1000 elderly
patients folowing general anesthesia: a randomized controlled study. Neural Regeneration
Research, 2009. 316-20.
34. Nishikawa, K.N., M.; Omote, K.; Namiki, A., Recovery characteristics and post-operative
delirium after long-duration laparoscope-assisted surgery in elderly patients: propofolbased vs. sevoflurane-based anesthesia. Acta Anaesthesiologica Scandinavica, 2004.
48(2): p. 162-8.
35. Papaioannou, A.F., O.; Michaloudis, D.; Balalis, C.; Askitopoulou, H., The impact of the
type of anaesthesia on cognitive status and delirium during the first postoperative days in
elderly patients. European Journal of Anaesthesiology, 2005. 22(7): p. 492-9.
36. Slor, C.J.d.J., J. F.; Vreeswijk, R.; Groot, E.; Ploeg, T. V.; van Gool, W. A.; Eikelenboom,
P.; Snoeck, M.; Schmand, B.; Kalisvaart, K. J., Anesthesia and postoperative delirium in
older adults undergoing hip surgery. Journal of the American Geriatrics Society, 1313.
59(7): p. 1313-9.
37. Berggren, D., et al., Postoperative confusion after anesthesia in elderly patients with
femoral neck fractures. Anesth Analg, 1987. 66(6): p. 497-504.
38. Kalisvaart, K.J.d.J., J. F.; Bogaards, M. J.; Vreeswijk, R.; Egberts, T. C.; Burger, B. J.;
Eikelenboom, P.; van Gool, W. A., Haloperidol prophylaxis for elderly hip-surgery patients
at risk for delirium: a randomized placebo-controlled study. Journal of the American
Geriatrics Society, 1658. 53(10): p. 1658-66.
39. Wang, W.L., H. L.; Wang, D. X.; Zhu, X.; Li, S. L.; Yao, G. Q.; Chen, K. S.; Gu, X. E.; Zhu,
S. N., Haloperidol prophylaxis decreases delirium incidence in elderly patients after
noncardiac surgery: a randomized controlled trial*. Critical Care Medicine, 2012. 40(3): p.
731-9.
40. Kaneko, T.C., J.; Ishikura, T.; Kobayashi, M.; Naka, T.; Kaibara, N. Prophylactic
consecutive administration of haloperidol can reduce the occurrence of postoperative
delirium in gastrointestinal surgery. Yonago Acta Medica, 1999. 179-184.
Page 22 of 24
41. Liptzin, B.L., A.; Garb, J. L.; Fingeroth, R.; Krushell, R., Donepezil in the prevention and
treatment of post-surgical delirium. American Journal of Geriatric Psychiatry, 1100. 13(12):
p. 1100-6.
42. Marcantonio, E.R.P., K.; Appleton, P.; Davis, R. B., Pilot randomized trial of donepezil
hydrochloride for delirium after hip fracture. Journal of the American Geriatrics Society,
2011. 59(2).
43. Sampson, E.L.R., P. R.; Ndhlovu, P. N.; Vallance, A.; Garlick, N.; Watts, J.; Blanchard, M.
R.; Bruce, A.; Blizard, R.; Ritchie, C. W., A randomized, double-blind, placebo-controlled
trial of donepezil hydrochloride (Aricept) for reducing the incidence of postoperative
delirium after elective total hip replacement. International Journal of Geriatric Psychiatry,
2007. 22(4): p. 343-9.
44. Akarsu, T.T., H.; Bolat, C.; Ozkaynak, I., Comparison of pre-emptive pregabalin with
placebo and diclofenac combination for postoperative analgesia and cognitive functions
after laparoscopic cholecystectomy. Turkiye Klinikleri Journal of Medical Sciences, 2012.
32 (4): p. 963-970.
45. Leung, J.M.S., L. P.; Rico, M.; Petersen, K. L.; Rowbotham, M. C.; Dahl, J. B.; Ames, C.;
Chou, D.; Weinstein, P. Pilot clinical trial of gabapentin to decrease postoperative delirium
in older patients. Neurology, 2006. 1251-3.
46. Ono, H.T., T.; Kido, Y.; Fujino, Y.; Doki, Y., The usefulness of bright light therapy for
patients after oesophagectomy. Intensive & Critical Care Nursing, 2011. 27(3): p. 158-66.
47. Taguchi, T.Y., M.; Kido, Y., Influence of bright light therapy on postoperative patients: a
pilot study. Intensive & Critical Care Nursing, 2007. 23(5): p. 289-97.
48. Sieber, F.E.Z., K. J.; Gottschalk, A.; Blute, M. R.; Lee, H. B.; Rosenberg, P. B.; Mears, S.
C., Sedation depth during spinal anesthesia and the development of postoperative delirium
in elderly patients undergoing hip fracture repair.[Erratum appears in Mayo Clin Proc. 2010
Apr;85(4):400 Note: Dosage error in article text]. Mayo Clinic Proceedings, 2010. 85(1): p.
18-26.
49. Mason, S.E., A. Noel-Storr, and C.W. Ritchie, The impact of general and regional
anesthesia on the incidence of post-operative cognitive dysfunction and post-operative
delirium: a systematic review with meta-analysis. J Alzheimers Dis, 2010. 22 Suppl 3: p.
67-79.
50. Teslyar, P., et al., Prophylaxis with antipsychotic medication reduces the risk of postoperative delirium in elderly patients: a meta-analysis. Psychosomatics, 2013. 54(2): p.
124-31.
51. Zhang, H., et al., Strategies for prevention of postoperative delirium: a systematic review
and meta-analysis of randomized trials. Crit Care, 2013. 17(2): p. R47.
52. Babar A. Khan, M., MS, Mohammed Zawahiri, MD,Noll L. Campbell, PharmD, and M. and
Malaz A. Boustani, MPH, Biomarkers for Delirium—A Review. Am Geriatr Soc., 2011.
59(2): p. 256-261.
53. Khan, B.A., et al., S100 calcium binding protein B as a biomarker of delirium duration in
the intensive care unit - an exploratory analysis. Int J Gen Med, 2013. 6: p. 855-61.
54. Zhongheng Zhang, M., Lifei Pan, MB, Hongsheng Deng, MM, Hongying Ni, MM, Xiao Xu,
MB, Prediction of delirium in critically ill patients with elevated C-reactive protein. Journal
of Critical Care, 29 (2014) 88–92. 29(1): p. 88-92.
55. AndreasBaranyi, M.D., M.A., Hans-Bernd Rothenhäusler, M.D., The impact of soluble
interleukin-2 receptor as a biomarker of delirium. Psychosomatics, 2014. 55(1): p. 51-60.
56. Kotaro Hatta a, Yasuhiro Kishi b, Takashi Takeuchi c, KenWada d, Toshinari Odawara e,
Chie Usui a, and H.N.g. Yutaka Machida f, for the DELIRIA-J Group, The predictive value
of a change in natural killer cell activity for delirium. Progress in NeuroPsychopharmacology & Biological Psychiatry, 2014. 48 (01): p. 26-31.
57. Krenk, L.R., L. S.; Hansen, T. B.; Bogo, S.; Soballe, K.; Kehlet, H., Delirium after fast-track
hip and knee arthroplasty. British Journal of Anaesthesia, 2012. 108(4): p. 607-11.
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