Delirium in Intensive Care Unit

Annoying facts.. Annoying disease
most common psychiatric
syndrome found in the general
hospital setting.
Upto 40% of hospitalized AIDS
patients
Upto 25% of hospitalized cancer
patients
Upto 51% of postoperative patients
up to 80% of mechanically
ventilated adult ICU patients

Usually followed treatment paths...
Sister, you give some fortwin-
phenergan
You call the duty doctor
What should I do.. Sister?..tell the
patient to be calm…
We are more tempted to label it as
an annoyance.....from the patient
And hesitant to accept
that…actually we are more
confused than the patient…!!! [ in
managing icu psychosis ]

limbs, heart or gall
bladder…medically or
surgically…but don’t ignore this
organ….Getting mentally disturbed….or
Getting physically
disturbed….which is more common
among us as a normal human
being or as a doctor…..?
it’s a problem anybody in this world
can develop, when diseased,
traumatized, with all psychological
defenses breached…

In a busy ICU, for the nursing staff
it’s a KATRINA
A reduced clarity of awareness
of the environment with reduced
ability to focus, sustain, or shift
attention.
A change in cognition (such as
Memory deficit, disOrientation,
Language disturbance) or
the development of a perceptual
disturbance

Other symptoms commonly
associated with delirium include..
emotional disturbances (i.e., fear,
anxiety, anger, depression, apathy,
euphoria)
attention deficits,
disordered sleep-wake cycle

Don’t miss the introverts
Hyperactive delirium is more often
associated with hallucinations and
delusions, while
hypoactive delirium is more often
characterized by confusion and
sedation, and is often
misdiagnosed in ICU patients.

Before the storm…
Some patients manifest subclinical
delirium or prodromal symptoms
such as restlessness,anxiety,
irritability, distractibility, or sleep
disturbance in the days before the
onset of overt delirium.
The duration of symptoms range
from less than 1 week to more than
2 months

To reach the other end
safely is difficult…
majority of patients recover fully,
delirium may progress to stupor,
coma, seizures, or death,
particularly if untreated.
Full recovery is less likely in the
elderly,
Persistent cognitive deficits are
also quite common in elderly

Risk Factors
preexisting dementia/cognitive impairment,
history of hypertension and/or alcoholism,
and a
high severity of illness at admission
severe sepsis or shock;
on mechanical ventilation;
receiving parenteral sedative and opioid
medications
Coma is an independent risk factor
Benzodiazepine use may be a risk factor
Age 65 years or older.
Current hip fracture

Notorious.....
Surgeries : particularly cardiotomy, hip
surgery, or a transplant
Burns
dialysis
central nervous system lesions

Dont disturb the equillibrium...further
Ohh…I lost it….I mean my acetyl choline
reserve…e.g. aging
Don’t drain my reserve with your naughty
drugs
Dementia
Male
Visual impairment

See.... that crooked fellow tied me, when I
was in ICU
The use of re-straints, including endotracheal
tubes ‘restraints, intravenous lines, bladder
catheters, and intermittent pneumatic leg
compression devices, casts, and traction
devices all have been associated with an
increased incidence of delirium

Sleep deprivation
may lead to the development of both
psychosis and delirium.
Studies have found that the average amount
of sleep in patients in an intensive care unit
(ICU) is limited to 1 hour and 51 minutes per
24-hour period

Work..tension..many find it
difficult to sleep @ home…then
what about patients in ICUs?
They have few complete sleep
cycles, numerous awakenings due
to environmental disruptions (noise,
light, and physical stimulation), and
infrequent REM sleep
Sleep deprivation impairs tissue
repair and cellular immune
function, and may affect the healing
response
In critically ill patients, sleep
deprivation may contribute to the
development of delirium and
increased levels of physiologic
stress

Risk Factors
Four baseline risk factors are positively and
significantly associated with the development
of delirium in the ICU: preexisting dementia,
history of hypertension and/or alcoholism,
and a high severity of illness at admission :
patients with a baseline history of cognitive
impairment, severe sepsis or shock; on
mechanical ventilation; receiving parenteral
sedative and opioid medications
Coma is an independent risk factor
Benzodiazepine use may be a risk factor

Impact of Delirium on ICU Patient
Outcomes
need to stay longer in hospital or in critical
care
have an increased incidence of dementia
have more hospital-acquired complications,
such as falls and pressure sores
have a very high rate of death during the
months following discharge; especially first 6
months
Increased cost of care

Impact of Delirium on
Outcomes
In postoperative patients, delirium is a
harbinger of limited recovery and poor long-
term outcome ; particularly after orthopedic
surgery
Seizures may occur in delirium, particularly
among patients with alcohol or sedative-
hypnotic withdrawal, head trauma,
hypoglycemia, strokes, or extensive burns

An can change
his/her life
Early detection and treatment of
delirium may in turn
allow for a patient to be conscious,
yet cooperative enough to
potentially participate in ventilator
weaning trials
and early mobilization efforts.

Delirium due to Drug and/or
Alcohol Withdrawal.
manifests as a hyperactive type of delirium
Withdrawal symptoms may result from
abrupt discontinuation of:
1) drugs that patients were taking chronically;
2) sedatives or opioids administered as part of
routine ICU care; or
3) chronic ethanol use.

Opioid Withdrawal....
sweating, piloerection, mydriasis,
lacrimation, rhinorrhea, vomiting, diarrhea,
abdominal cramping, tachycardia,
hypertension, fever, tachypnea, yawning,
restlessness, irritability, myalgias, increased
sensitivity to pain, and anxiety
The onset of symptoms can occur < 12 hrs
following discontinuation of opioids, or be

Benzodiazepine withdrawal
Prolonged benzodiazepine use in ICU
patients may lead to withdrawal symptoms
when the drug is abruptly discontinued
manifesting as anxiety, agitation, tremors,
headaches, sweating, insomnia, nausea,
vomiting, myoclonus, muscle cramps,
hyperactive delirium, and occasionally
seizures
flumazenil may induce symptoms of
benzodiazepine withdrawal
Don’t
leave me

Even dexmedetomidine....
Adult ICU patients receiving
dexmedetomidine infusions for up to 7 days
have developed withdrawal symptoms, most
commonly nausea, vomiting, and agitation,
within 24–48 hrs of discontinuing
dexmedetomidine
the incidence of withdrawal following
discontinuation of dexmedetomidine was
4.9% vs. 8.2% in midazolam-treated patients

Alcohol Withdrawal Syndrome
[AWS]
Between 8% and 31% of hospitalized
patients with ethanol dependence, especially
surgical and trauma patients, will go on to
develop (AWS)
generalized tonic-clonic seizures, delirium
tremens (DTs), (agitation, delirium, and
seizures) and hyperadrenergic symptoms
(hypertension, tachycardia, arrhythmias)
may exhibit prolonged ventilator dependence
and extended ICU stays as a result of

So dont miss....
Signs and symptoms of opioid and sedative
withdrawal in critically ill patients may be
overlooked or attributed to other causes,
such as alcohol or illicit drug withdrawal.
opioids and/or sedatives administered for
prolonged periods (i.e., days) should be
weaned over several days in order to reduce
the risk of drug withdrawal.

Approaches in prevention
nonpharmacologic (e.g., early mobilization),
pharmacologic, and
combined pharmacologic/nonpharmacologic
approaches.

Trials say....
no recommendation for using a
pharmacologic delirium prevention
protocol [administering prophylactic
antipsychotics to the general ICU population]
in adult ICU patients
Early and aggressive mobilization may
reduce the incidence and duration of
delirium, shorten ICU and hospital LOS, and
lower hospital costs.

Dear..You want GOOD KNIGHT ?
nurses should select time periods
to promote sleep by avoiding
routine ICU care activities (such as
the daily bath), turning down the
lights, and reducing ambient noise
during these periods
 In three studies suggesting
scheduled rest periods, the periods
most likely to be uninterrupted in
the ICU were 2–4 AM, 12–5 AM
and around 3 AM

GOOD NIGHT.......dear
Control daytime light exposure,
use eye patches or ear plugs to
limit the aversive effects of noise
and light
cluster patient care activities,
and decrease stimuli at night to
protect patients' sleep cycles
no recommendation for using
specific modes of mechanical
ventilation to promote sleep in adult
ICU patients

To catch the thief, you… he has to
be responsive
patients should be able to
sufficiently interact and
communicate
Optimal pain management and a
light level of sedation are essential
for this to occur.

Light and deep
Sedatives can be titrated to maintain either
light (i.e., patient is arousable and able to
purposefully follow simple commands) or
deep sedation (i.e., patient is unresponsive
to painful stimuli).
Multiple studies have demonstrated the
negative consequences of prolonged, deep
sedation, and the benefits of maintaining
lighter sedation levels in adult ICU patients

Light light light...
Maintaining light levels of sedation increases
the physiologic stress response, but is not
associated with an increased incidence of
myocardial ischemia (B).
So the recommendation is that sedative
medications be titrated to maintain a light
rather than deep level of sedation in adult
ICU patients, unless clinically
contraindicated
daily sedation interruption or a light target
level of sedation

Don’t knock him/her out....if
possible
Check patient’s ability to
purposefully respond to commands
(i.e., a combination of any three of
the following actions) upon request
open eyes, maintain eye contact,
squeeze hand, stick out tongue,
and wiggle toes
is essential, for assessing patients’
readiness to wean and extubate,
for performing delirium
assessments, and for implementing
early mobility efforts.

Analgesia-first sedation
 in mechanically ventilated adult
ICU patients
high frequency of pain and
discomfort as primary causes of
agitation; patients should receive
adequate and preemptive
treatment for pain
is associated with longer ventilator-
free time

Analgesia-first sedation
But opiates can interfere with
respiratory drive, reduce gastric
motility, and complicate the
provision of enteral nutrition
Possible pain recurrence and
withdrawal upon analgesic
discontinuation
 may require supplementation with
other traditional sedative agents

Other points
Restraints themselves can increase agitation
and should be considered only when other
means of control are not effective or
appropriate
The justification for initiating restraints and
continuing use of restraints should be
documented
Education of nursing staff on each shift
regarding the clinical features and course of
delirium
behavioral problems may make us to

DELIRIUM
MONITORING SCALES
AND SEDATION
SCALES
.

Routine monitoring of delirium in
adult ICU patients is feasible in
clinical practice
ICU patients at moderate to high risk for
delirium (e.g.,) should be routinely
monitored, at least once per nursing shift, for
the development of delirium using a valid
and reliable delirium assessment tool.
 The Confusion Assessment Method for the
ICU (CAM-ICU) and the Intensive Care
Delirium Screening Checklist (ICDSC) are
the most valid and reliable delirium
monitoring tools in adult ICU patients

Monitoring depth of sedation
The use of sedation scales,
sedation protocols designed to minimize
sedative use, and
the use of nonbenzodiazepine medications
are associated with improved ICU patient
outcomes, and decreased incidences of
delirium and long-term cognitive dysfunction

The Richmond Agitation-Sedation Scale
(RASS) and Sedation-Agitation Scale (SAS)
are the most valid and reliable sedation
assessment tools for measuring quality and
depth of sedation in adult ICU patients
objective measures of brain function (e.g.,
AEPs, BIS, NI, PSI, or SE) be used as an
adjunct to subjective sedation assessments
in adult ICU patients who are receiving
neuromuscular blocking agents

EEG monitoring if known or suspected
seizures, to titrate electrosuppressive
medication to achieve burst suppression in
adult ICU patients with elevated ICP
Useful in ICU patients either with known
seizure activity or who are at risk for seizures
(e.g., traumatic brain injury, intracerebral
hemorrhage, CVA)

PSYCHIATRIC MANAGEMENT
Coordinate with other physicians caring for
the patient
Identify the etiology
Initiate interventions for acute conditions
Provide other disorder-specific treatment
Assess and monitor psychiatric status
Educate patient and family regarding the
illness
Provide postdelirium management

ENVIRONMENTAL AND
SUPPORTIVE
INTERVENTIONS
understimulation is also dangerous;
gprovide a regular amount of
modest stimulation (vocal, visual,

ENVIRONMENTAL AND
SUPPORTIVE
INTERVENTIONS [nice]introducing cognitively stimulating
activities
Address dehydration
optimise oxygen saturation
Address infection
avoid unnecessary catheterisation
mobilise soon after surgery
dentures, ensuring they fit properly
Any medication or agent known to
cause delirium or to have high

SOMATIC INTERVENTIONS
There is no published evidence that
treatment with haloperidol reduces the
duration of delirium in adult ICU patients
Atypical antipsychotics may reduce the
duration of delirium in adult ICU patients
No recommendations for administering
rivastigmine to reduce the duration of
delirium in ICU patients (–1B).
Benzodiazepines are considered the
mainstay in alcohol withdrawal

Benzodiazepines
anxiolytic, amnestic, sedating, hypnotic, and
anticonvulsant effects, but no analgesic
activity
Their amnestic effects extend beyond their
sedative effects
Lorazepam > midazolam > diazepam.
when there is a need for a medication that
can raise the seizure threshold (unlike
antipsychotics, which lower the seizure
threshold)
contraindicated in delirium from hepatic

DOUBLE EDGED
Benzodiazepines can exacerbate symptoms
of delirium
when used alone for general cases of
delirium shown to be ineffective
Combining a benzodiazepine with an
antipsychotic medication  for patients who
can only tolerate lower doses of
antipsychotic medications or who have
prominent anxiety or agitation.
In hepatic insufficiency: if bzd is needed, use

Side effects
behavioral disinhibition, amnesia, ataxia,
respiratory depression, physical
dependence, rebound insomnia, withdrawal
reactions, and delirium
Be vigilant : Elderly patients, respiratory
depression , systemic hypotension, hepatic
dysfunction
Parenteral formulations of lorazepam :

Butyrophenones
Haloperidol, a high-potency dopamine-
blocking agent is most frequently used
because of its short half-life, few or no
anticholinergic side effects, no active
metabolites, and lower likelihood of causing
sedation.
orally or intramuscularly,
fewer extrapyramidal side effects when
administered intravenously.
Pharmakokinetics safe in hepatic

Haloperidol
Optimal dose range : initial doses of
haloperidol in the range of 1–2 mg every 2–4
hours as needed have been used, and even
lower starting doses (e.g., 0.25–0.50 mg
every 4 hours as needed) are suggested for
elderly patients.
Initiating haloperidol with a bolus dose of 10
mg followed by continuous intravenous
infusion of 5–10 mg/hour has been
suggested

Dosing pattern
combination of antipsychotics and
benzodiazepines is more efficacious
Started with 3 mg i.v. of haloperidol followed
immediately by 0.5–1.0 mg i.v. of lorazepam.
if little or no improvement is observed within
20 minutes, an additional
dose of 5 mg i.v. of haloperidol and 0.5–2.0
mg i.v. of lorazepam can be given

Cholinergics
anticholinergic mechanisms may be involved
in delirium from hypoxia, hypoglycemia,
thiamine deficiency, traumatic brain injury,
and stroke
Physostigmine reversed the delirium
resulting from ranitidine , homatropine
eyedrops , benztropine , and meperidine .
Iv /im 0.16 to 2.00 mg and continuous
intravenous infusions of 3 mg/hour

Other drugs
Consider giving short-term (usually for 1
week or less) haloperidol or olanzapine
[NICE –guidelines 2010]
Phenothiazines : prototype- Chlorpromazine

Side effects in general
extrapyramidal side effects, tardive
dyskinesia, and neuroleptic malignant
syndrome.
Lengthen the QT interval
lowering of the seizure threshold,
galactorrhea, elevations in liver enzyme
levels
Phenothiazines can be associated with
sedation, anticholinergic effects, and α-
adrenergic blocking effects that can cause
hypotension

Wait....wait...
Dont use antipsychotics in patients at
significant risk for torsades de pointes (i.e.,
patients with baseline prolongation of QT
interval, patients receiving concomitant
medications known to prolong the QT
interval, or patients with a history of this
arrhythmia)
Haloperidol, Ziprasidone, risperidone [four
out of 1,100 patients]

QuesT
The ECG should be monitored in patients
receiving antipsychotic medications for
delirium, and a QTc interval longer than 450
msec or more than 25% over baseline may
warrant a cardiology consultation and
consideration of discontinuation of the
antipsychotic medication.
 serum levels of magnesium and potassium

Milk
My name is Propofol and I love GABAA,
glycine, nicotinic, and M1 muscarinic
receptors
sedative, hypnotic, anxiolytic, amnestic,
antiemetic, and anticonvulsant properties
amnestic effects at light sedation levels are
less than that of benzodiazepines
Rapid onset and offset
 useful in patients requiring frequent
awakenings for neurologic assessments and
it may facilitate daily sedation interruption
protocols

Spoilt Milk
dose-dependent respiratory depression and
hypotension
propofol infusion syndrome (PRIS)
propofol infusion syndrome [PRIS]
worsening metabolic acidosis
Hypertriglyceridemia
hypotension with increasing vasopressor requirements
Arrhythmias
Acute kidney injury
hyperkalemia
rhabdomyolysis
liver dysfunction
[usually associated with prolonged administration of high
propofol doses (> 70 μg/kg/min)]

Such an agent will
be a very valuable
addition...
Sedation
Analgesia
Reduce delirium incidence
Easy awakening for assessment
Minimal respiratory depression

Dexmedetomidine
⍺2 Agonist-- sedative, analgesic/opioid
sparing [reduce opioid requirements in
critically ill patients], and sympatholytic
properties
Patients are more easily arousable and
interactive
The onset of sedation occurs within 15 mins
and peak sedation occurs within 1 hr of
starting an IV infusion of dexmedetomidine
1 mcg/kg loading dose, administered over 10

Dexmedetomidine
metabolized by the liver -- hepatic
dysfunction: prolonged emergence, require
lower dexmedetomidine doses
Although dexmedetomidine has only been
approved in the United States for short-term
sedation of ICU patients (< 24 hrs) at a
maximal dose of 0.7 μg/kg/hr (up to 1.0
μg/kg/h for procedural sedation), several
studies demonstrate the safety and efficacy
of dexmedetomidine infusions administered
for greater than 24 hrs (up to 28 days) and at
higher doses (up to 1.5 μg/kg/hr)

2013 guidelines by the Society of
Critical Care Medicine
in adult ICU patients with delirium unrelated
to alcohol or benzodiazepine withdrawal,
continuous IV infusions of dexmedetomidine
rather than benzodiazepine infusions be
administered for sedation in order to reduce
the duration of delirium in these patients
benzodiazepines may be a risk factor for the
development of delirium in the ICU.

Zhang et al. Critical Care 2013,
17:R47
The limited data suggested that the
efficacious way to prevent postoperative
delirium included dexmedetomidine
sedation, multicomponent interventions and
antipsychotics comprising haloperidol,
olanzapine and risperidone

Jose´ R. Maldonado, M.D.,
(Psychosomatics 2009; 50:206 –217)
Dexmedetomidine and the Reduction of
Postoperative Delirium after Cardiac Surgery
“…suggest that postoperative sedation with
dexmedetomidine was associated with
significantly lower rates of postoperative
delirium and lower care costs”

Bad habits of this good friend..
hypotension and bradycardia
 IV loading doses can cause either
hypotension or hypertension
Because dexmedetomidine does not
significantly affect respiratory drive, it is the
only sedative approved in the United States
for administration in nonintubated ICU
patients, and infusions can be continued as
needed following extubation
[but beware of upper airway obstruction]

Which agent to use
Sedation strategies using
nonbenzodiazepine sedatives (either
propofol or dexmedetomidine) may be
preferred over sedation with
benzodiazepines (either midazolam or
lorazepam) to improve clinical outcomes in
mechanically ventilated adult ICU patients
The clinical significance of the comparative
deliriogenic effects .... one high-quality trial
indicating benzodiazepines pose higher risks

Technology has reached its peak ;
still in some situations....
benzodiazepines remain important for
managing agitation in ICU patients,
especially for treating anxiety, seizures, and
alcohol or benzodiazepine withdrawal.
 Benzodiazepines are also important when
deep sedation, amnesia, or combination
therapy to reduce the use of other sedative
agents is required

Print master
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Special situations
When delirium is comorbid with
other psychiatric disorders, the
delirium should be treated first
and the treatments for these
other disorders, such as
antidepressant or anxiolytic
medications, should be minimized
or not begun until the delirium is
resolved
It can be difficult to distinguish
between delirium and dementia

Special situations
Use antipsychotic drugs with
caution or not at all for people
with conditions such as
Parkinson's disease

References
 2013 guidelines by the Society of
Critical Care Medicine
 American Psychiatric Association
steering committee on practice
guidelines For the Treatment of patients
with Delirium [APA Practice
Guidelines],1999
 Delirium Diagnosis, prevention and
management,Issued: July 2010; NICE
clinical guideline 103,
guidance.nice.org.uk/cg103

Delirium in Intensive Care Unit

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Delirium in Intensive Care Unit