3. Delirium
• An acute, fluctuating neurobehavioral syndrome
caused by the disruption of neuronal activity
secondary to systemic disturbances.
Maldonado, José R. (2013). Neuropathogenesis of Delirium: Review of Current Etiologic Theories and Common Pathways.
The American Journal of Geriatric Psychiatry, 21(12), 1190–1222. doi:10.1016/j.jagp.2013.09.005
4. Epidemiology
Population Prevalence
Elderly 1-2% in community sample
Emergency department 18-35%(on admission)
Post OP delirium 15-53% (after high risk surgery)
Inpatients 29-64%
ICU 70-87% (in those requiring
mechanical ventilation)
5. Burden of Delirium:
• Increased nursing care
• Increased length of stay
• Increased risk of cognitive decline
• Increased risk of functional decline
• Increased mortality
• Delay in postoperative mobilization
• Prevention of early rehabilitation
• Increased rate of nursing home placement
• Increased need for home care services
• Increased distress to caregivers
• Barrier to psychosocial closure in terminally ill patient
12. Excess Glutamate
NMDA
(Through its excitatory
neurotoxicity effects)
Neuronal death
DELIRIUM
NMDA antagonists,
such as ketamine
and phencyclidine
(PCP),
Ca+2
Activation of
phosholipases,
endonucleases and
proteases
Damage of cell structures-
cytoskeleton, DNA
17. Chronic stress (illness/trauma)
Activates sympathetic system, HPA axis
Increased cytokine secretion (IL-1,2,&6), TNF, and
interferon at the level of cerebrum (activation of microglia)
and chronic hypercortisolism.
Deleterious effect on Hippocampal 5HT1a Receptors
Occurrence of delirium
18.
19. Neuronal aging hypothesis
• The NAH suggests that the aging process and
accompanying physiologic changes constitute
an independent risk factor for delirium.
• Accordingly, aging is associated with age-
related cerebral changes in stress-regulating
neurotransmitters, brain blood flow decline,
decreased vascular density, neuron loss
(particularly in locus coeruleus and substantia
nigra), and intracellular signal transduction
systems.
20. • This likely explains why then aging process itself is
associated with some degree of cognitive deficits
and an increased risk of dementia
• The NAH may also explain why the elderly seem
to experience a greater chance of developing
delirium when challenged by physiologic distress
that is better tolerated by younger individuals.
• An estimation of the probability of transitioning to
delirium by age indicates that the incremental risk
is large for patients aged 65 years and older. The
probability of transitioning to delirium increased
dramatically(by 2%) for each year of life after 65
years.
21. Neuronal oxidative stress
• Hypoperfusion appears to induce chronic
oxidative damage in tissues and cells, largely
due to the generation of reactive oxygen and
reactive nitrogen species.
• Any condition that outpaces the capacity of
endogenous redox systems to neutralize such
toxic intermediates could lead to a system
imbalance or to major compensatory
adjustments that rebalance the system. This
new redox state is generally referred to as
“oxidative stress”
22. • The Oxidative Stress Hypothesis (OSH), initially
proposed by Engel and Romano, proposes that a
number of physiologic processes, such as tissue
damage, hypoxia, severe illness, and infections,
may give rise to increased oxygen consumption
and/or decreased oxygen availability, with
associated increased energy expenditure and
reduced cerebral oxidative metabolism, leading to
cerebral dysfunction and associated cognitive and
behavioral symptoms of delirium.
23. DIURNAL DYSREGULATION
• This hypothesis suggests that disruptions to the
24-hour circadian cycle and the usual stages of
sleep may lead to disturbances in the integrity of
sleep and the physiologic sleep architecture.
• Hospitalized patients experience severe
alterations of the sleep wake cycle with sleep
loss, sleep fragmentation, and sleep wake cycle
disorganization.
24. • Studies have demonstrated a relationship
between an irregular melatonin circadian rhythm
(i.e., abnormally low serum levels of melatonin)
and postoperative delirium.
• It`s been found sleep deprivation to consistently
precede onset of delirium in postsurgical cardiac
patients and that ICU patients with sleep
deprivation were significantly more likely to
develop delirium than patients without sleep
deprivation.
25.
26. • The administration of melatonin in ICU patients
has been shown to improve quality of sleep and
prolongation of sleep time, whereas others
demonstrated that the prophylactic
administration of low-dose exogenous melatonin
may decrease the incidence of delirium.
• Finally, data suggest that the use of
prophylactic melatonin decreases the incidence
and severity of “sundowning” and agitated
behavior in elderly, demented individuals.
27. Network connectivity
• The Network Disconnectivity Hypothesis (NDH)
suggests that the heterogenicity of delirium
presentations is better explained by the action of
various factors (e.g., drugs or toxins) acting on
specific brain neurochemical systems.
• NDH suggests that the failure (e.g., hypo- or
hyperactivity) of one system will undoubtedly
affect others (i.e., the connectivity principle).
28. • NDH proposes that delirium results from an
acute breakdown in network connectivity within
the brain.
• Furthermore, the NDH suggests that two
important factors determine a subject’s
vulnerability to delirium:
(1) the baseline network connectivity
(defined as the connectivity of neural networks
within the brain before the precipitating insult
provoking delirium), which is influenced by most
recognized nonmodifiable delirium risk factors
(e.g.,age, baseline level of cognitive functioning),
29. (2) the level of inhibitory tone, which will
determine the degree of change in network
connectivity and is influenced by modifiable
risk factors (e.g., metabolic abnormalities,
sleep deprivation, infection and
inflammation, medication such as
benzodiazepines).
• The model suggests that when these two
factors affect separate neuronal networks, to
different degrees, they produce the various
motoric phenotypes described (e.g.,
hyperactive, hypoactive,mixed).
30. • Thus, the form of delirium that ensues will
depend on how and which networks breaks down
(dependent on both the individual’s baseline
network connectivity and the degree of change in
inhibitory tone produced).
37. • If the patient is highly vulnerable, possibly a
patient with advanced dementia, smaller
disturbances such as constipation, dehydration,
sleep deprivation, urinary retention, or minor
medical procedures can also precipitate
delirium.
• The nature of delirium is transient but can persist
in patients with predisposing factors.
• A systematic review showed that hospital
delirium persisted to the time of discharge in
45% of cases and persisted one month later in
33% of cases.
Ramírez Echeverría MdL, Schoo C, Paul M. Delirium. [Updated 2022 Nov 19].
Treasure Island (FL): StatPearls Publishing; 2022 Jan.
38. References
• KAPLAN & SADOCK’S COMPREHENSIVE
TEXTBOOK OF PSYCHIATRY
• Maldonado, José R. (2013). Neuropathogenesis
of Delirium: Review of Current Etiologic Theories
and Common Pathways. The American Journal
of Geriatric Psychiatry, 21(12), 1190–1222.
doi:10.1016/j.jagp.2013.09.005
39. • Ramírez Echeverría MdL, Schoo C, Paul
M. Delirium. [Updated 2022 Nov 19].
Treasure Island (FL): StatPearls
Publishing; 2022 Jan.
• B.J.A. Palanca, T.S. Wildes, Y.S. Ju, S.
Ching, M.S.
Avidan,Electroencephalography and
delirium in the postoperative period,British
Journal of Anaesthesia,Volume 119, Issue
2,2017.
the study of abnormal changes in body functions that are the causes, consequences, or concomitants of disease processes. a branch of the life sciences that deals with the anatomy, physiology, and pathology of the nervous system.
Stay?
CHOINERGIC AND ANTI CHOINERGIC DRUGS. Extensive evidence supports the role of cholinergic deficiency. cholinesterase inhibitors appear to have some benefit even in cases of delirium that are not induced by drugs.Amitryptyline most ach protryptyine second.paroxetine most ach.
CHOINERGIC AND ANTI CHOINERGIC DRUGS. Extensive evidence supports the role of cholinergic deficiency. cholinesterase inhibitors appear to have some benefit even in cases of delirium that are not induced by drugs.Amitryptyline most ach protryptyine second.paroxetine most ach.
MAY CAUSE NEURONA DEATH. Seen excess gutamate in traumatic brain inury, neurodegenerative diseases-wernickes encehaopathy, alcoholism and alcohol withdrawal, severe dehydration and hypoglycemia. Status epilepticus can occur due to build up of glutamate.
an inhibitor of brain activity, has been implicated in contributing to delirium secondary to benzodiazepine and alcohol withdrawal. aggravate astrocyte swelling that initiate a cascade of events leading to delirium
Hpa axis functions. Cytokines(IL-1,2,&6), TNF, and interferon, may contribute increasing the permeability of the blood–brain barrier and altering neurotransmission.
