Delirium is a disturbance of consciousness and cognition characterized by acute onset and fluctuating course. It commonly occurs in the intensive care unit (ICU), with a prevalence of 32.3% among ICU patients. The three main subtypes are hypoactive, hyperactive, and mixed delirium. Potential causes of delirium include neurotransmitter imbalances, inflammation, impaired oxidative metabolism, and alterations in amino acid transport. Risk factors include older age, cognitive impairment, and medications such as benzodiazepines. Delirium is diagnosed using tools such as the Confusion Assessment Method for the ICU and managed through both nonpharmacological and pharmacological interventions.

1. Dr. Parag Moon
Senior resident
Dept. of Neurology
GMC, Kota.

2.  Defined by Diagnostic and Statistical Manual
of Mental Disorders(DSM)-IV
 Disturbance of consciousness and cognition
that develops over short period of time
(hours to days) and fluctuates over time.
 Three subtypes of delirium: hyperactive,
hypoactive, and mixed

3.  Hypoactive delirium-decreased
responsiveness, withdrawal, apathy.
 Hyperactive delirium-agitation, restlessness,
and emotional lability.
 Mixed.

4.  Prevalence of delirium in ICU was 32.3%.
 Incidence of delirium in ICU ranges from 45%
to 87%.
 Incidence appears to vary according to
mechanically ventilated patients.
 20% in nonintubated ICU patients
 83% in mechanically ventilated patients.

5.  Hyperactive delirium rare (1.6%).
 Hypoactive delirium-43.5%
 Mixed delirium-54.1%
 Hypoactive delirium more frequently in older
patients and has worse prognosis.
 Prolonged periods of ICU delirium associated
with increased risk for long-term cognitive
impairment at 3 months.

6.  Poorly understood.
1. Neurotransmitter imbalance
 Imbalances in synthesis, release, and inactivation
of neurotransmitters that normally control
cognitive function, behavior, and mood.
 Greatest focus given to dopamine and
acetylcholine.
 Imbalance in one or both results in neuronal
instability and unpredictable neurotransmission.
 Excess of dopamine or depletion of acetylcholine.
 Other neurotransmitters- γ- aminobutyric acid
(GABA), serotonin, endorphins, glutamate

7. 2. Inflammation
 Inflammatory abnormalities induced by
endotoxin and cytokines probably contributes
 Tumor necrosis factor-α, interleukin-1,other
cytokines and chemokines initiate cascade of
endothelial damage, thrombin formation, and
microvascular compromise
 May incite brain dysfunction by decreasing
cerebral blood flow via formation of
microaggregates of fibrin, platelets, neutrophils,
and erythrocytes in cerebral microvasculature.

8.  Constricting cerebral vasculature-activation
of α1-adrenoceptors
 Interfering with neurotransmitter synthesis
and neurotransmission
 Inflammatory mediators cross blood-brain
barrier, increase vascular permeability,
 Blunted anti-inflammatory response

9.  Higher plasma concentrations tumor necrosis
factor receptor-1, and lower plasma
concentrations of protein C, matrix
metalloproteinase-9 were associated with
increased risk of delirium

10. 3. Impaired oxidative metabolism
 Delirium as behavioral manifestation of
‘widespread reduction of cerebral oxidative
metabolism resulting in imbalance of
neurotransmission’.
 Engel and Romano believed diffuse slowing
on EEG to represent a reduction in brain
metabolism.
 Oxidative stress responsible for multi-organ
dysfunction in critically ill patients.

11. 4. Availability of large neutral amino acids
 Neurotransmitter levels and function affected
by changes in plasma concentrations of
various amino acid precursors
 Proposed that altered availability of large
neutral amino acids contributes to
development of delirium.
 Amino acid entry into brain regulated by
sodium-independent large neutral amino acid
transporter type 1 (LAT1).

12.  Tryptophan, essential amino acid and precursor
for serotonin, competes with large neutral amino
acids (for eg, tyrosine, phenylalanine, valine,
leucine, and isoleucine) for transport across BBB
via LAT1.
 Phenylalanine competes with large neutral amino
acids
 Increased cerebral uptake of tryptophan and
phenylalanine, compared with other large neutral
amino acids, leads to elevated levels of dopamine
and norepinephrine (noradrenaline).

13.  Predisposing factors (host factors)
 Present before ICU admission
1. Age
2. Alcoholism
3. Smoking
4. Hypertension
5. APOE4 polymorphism
6. Cognitive impairment
7. Hearing/visual impairment
8. Depression

14.  Precipitating factors.
 Occur during course of critical illness
 May involve factors of acute illness or be
iatrogenic;
 Represent potential preventive or therapeutic
intervention.

15.  Factors of critical
illness
1. Acidosis
2. Anemia
3. Infection/sepsis
4. Hypotension
5. Metabolic
disturbances
6. Respiratory disease
7. High severity of
illness
 Iatrogenic factors
1. Immobilization
2. Medication (opoids,
BDZ)
3. Sleep disturbances

16.  Pandharipande et al (2006) fpund patients
treated with lorazepam were more likely to be
delirious
 Treatment with fentanyl, morphine, propofol
were not significantly associated with
transition to delirium.
 Sedative agents that are GABA receptor
sparing (Opioids, dexmedetomidine (a novel
α2-receptor agonist) may reduce risk for
delirium in ICU patients as compared to BZD

17.  ICU patients sleep only 2 hours per day, less
than 6% of their sleep
 Sleep deprivation impairs cognition
 Factors affecting sleep-metabolic
derangements, mechanical ventilation,
exposure to sedative, analgesic medications
 Excessive noise and patient care activities-
minor role.

18.  Constellation of symptoms with acute onset
and fluctuating course
 Cognitive symptoms-disorientation, inability
to sustain attention, impaired short-term
memory, impaired visuospatial ability,
reduced level of consciousness,
perseveration.
 Behavioral symptoms-sleep-wake cycle
disturbance, irritability, hallucinations,
delusions

19.  Clinical manifestations vary according to
precipitating factors.
 For eg. Bacteremia present with
encephalopathy and declined mental status
and with alcohol withdrawal syndrome
present with symptoms of overactive
sympathetic central nervous system.

20.  Intensive Care Delirium Screening Checklist
(ICDSC) and the Confusion Assessment
Method for the ICU (CAM-ICU)
 Using ICDSC, each patient is assigned a score
from 0 to 8; a cut-off score of 4 has
sensitivity 99% and specificity 64% for
identifying delirium

22.  CAM-ICU has a more modest sensitivity
ranging from 64% to 81%, high specificity
from 88% to 98%.

24.  S100B protein indicator of glial activation
and/or death
 Shown to be elevated in patients with
delirium
 Higher baseline levels of procalcitonin or C-
reactive protein were associated with more
days with delirium
 Other biomarkers elevated-brain-derived
neurotrophic factor, neuron-specific enolase,
interleukins, cortisol

25.  Multicomponent strategies
 Repeated reorientation of patient
 Provision of cognitively stimulating activities
 Nonpharmacologic sleep protocol
 Intermittent boluses rather than continuous
infusions
 Promoting daily interruption of sedatives and
analgesics

26.  Early mobilization activities and range of
motion exercises
 Timely removal of catheters and physical
restraints
 Use of eyeglasses, magnifying lenses, and
hearing aids, ear plugs.
 Early correction of dehydration.
 Correction of infection, electrolyte imbalance

27.  First address complication of critical illness
that may lead to delirium (hypoxia,
hypercapnia, hypoglycemia, shock)
 Any drug intended to improve cognition may
have adverse psychoactive effects thus
paradoxically exacerbating delirium.

28.  Haloperidol recommended as drug of choice
for treatment of ICU delirium by SCCM
 Blocks D2 dopamine receptors, resulting in
amelioration of hallucinations, delusions,
unstructured thought patterns
 SCCM guidelines-hyperactive delirium to be
treated with 2 mg intravenously, followed by
repeated doses (doubling previous dose)
every 15 to 20 minutes while agitation
persists

29.  Once agitation subsides scheduled doses
(every 4 to 6 hours) may be continued for few
days, followed by tapered doses for several
days.
 Common doses for ICU patients range from 4
to 20 mg/day

30.  Atypical antipsychotics (risperidone,
ziprasidone, quetiapine, olanzapine) may also
be helpful in delirium.
 Skrobik et al (2004) compared olanzapine
with haloperidol and reported that resolution
of delirium symptoms was similar in both but
more side effects were observed in
haloperidol
 Medications should be avoided in with
prolonged QT intervals

31.  Dexmedetomidine, novel α2- receptor
agonist that does not act on GABA receptors,
may to be alternative sedative agent less
likely to cause delirium.
 Pandharipande P. et al (2007) showed ICU
patients sedated with dexmedetomidine
spent fewer days in coma and more days
neurologically normal than lorazepam.
 Benzodiazepines are not recommended for
management of delirium

33.  Delirium is associated with 3.2-fold increase
in 6-month mortality and 2-fold increase in
hospital stay duration.
 Also dependent on duration.
 Increasing duration of delirium was
independently associated with cognitive
impairment

35. Thank you

36.  Delirium in the intensive care unit;Timothy D
Girard, Pratik P Pandharipande, E Wesley;
Critical Care 2008, 12(Suppl 3):S3
 Delirium in the ICU: an overview:Rodrigo
Cavallazzi1, Mohamed Saad, Paul E Marik;
Annals of Intensive Care 2012, 2:49
 Delirium Management In The Icu; Department
of Surgical Education, Orlando Regional
Medical Center;approved in 04/2011
 SCCM guidelines for management of Delirium
in ICU.