Delirium

Pharmacological Management of Delirium

Antipsychotic Drugs ◦ Low dose haloperidol ◦ Atypical antipsychotics Increased risk of mortality with atypical antipsychotic drug use Non-pharmacological therapies should always be attempted first

Delirium prevention Cognitive Impairment Sleep Deprivation Immobility Visual Impairment Hearing Impairment Dehydration

Orientation Protocol Therapeutic Activities Protocol Non-pharmacological Sleep Protocol /sleep Enhancement Protocol Early Mobilization Protocol Vision Protocol Hearing Protocol Dehydration Protocol

why associated with dementia?

'old age' - LOC is remained, alterations is absent/mild and rarely have fluctuation in cognitive function

Dementia -onset -course -progression -duration -awareness -orientation -alertness -orientation -memory -thinking -perception

- -chronic, insidious -Long, symptoms progressive yet stable over time, no diurnal effects -slow but even -months to years -clear -generally normal -generally normal may be impaired -impaired - recent and remote -thoughts impoverished words difficult to find, poor judgment -misperceptions often absent

Delirium -onset -course -progression -duration -awareness -orientation -alertness -orientation -memory -thinking -perception

- -onset -short,diurnal; worse at night/awakening -abrupt -hrs to less than 1 month -reduced -fluctuates:lethargic or hyper -impaired, fluctuates -impaired, fluctuates -impaired- recent and immediate -disorganized, distorted, fragmented, -distorted, hallucination

causes of manifestations: -acute onset -fluctuation -inattention -disorganized thinking -altered level of c

-cognitive deficit -perceptual deficit -psychomotor deficit -altered sleep wake -emotion disturbances

Diagnostic Criteria for Delirium (4)

-Disturbance of consciousness (e.g., reduced clarity of awareness) 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 that is not better accounted for by a preexisting, established or evolving dementia -The disturbance develops over a short period of time (usually hours to days) and tends to fluctuate during the course of the day -There is evidence from the history, physical examination or laboratory findings that the disturbance is caused by the direct physiological consequences of a general medical condition

Depression -onset -course -progression -duration -awareness -orientation -alertness -orientation -memory -thinking -perception

-coincides with life changes, often abrupt -diurnal effects(worsen in the morning) -variable -at least 2 weeks -clear -normal -minimal impairment -selective disorientation -selective or patchy -intact but with themes of hopelessness or self-deprecation intact: delusion and hallucinations absent except in severe cases -

Delirium symptoms

-fluctuate -medication surgery, medica illness

Pathophysiology of Delirium Pathophysiology of delirium is poorly understood (WHY?)

-◦ Inattention and impaired cognition are difficult to define ◦ Fluctuating course is a hallmark feature of the disease ◦ Multiple and interacting risk factors ◦ Inaccessibility of the central nervous system to scientific investigation

Clinical Features of Delirium

1. Acute Onset 2. Fluctuating Course 3. Inattention 4. Disorganized Thinking 5. Altered level of consciousness 6. Cognitive deficits 7.x Perceptual disturbances 8. Psychomotor Disturbances 9. Altered sleep-wake cycles 10. Emotional disturbances

CBF decreases by>

42% -causes inattention and dec. cognition impairs o2 and glucose

genetic

APOE - important in myelin growth glucocorticoid receptor dopamine transporter/recepter TLR-4 (drive the inflammatory response by microglial cells)

Delirium

Abnormal mental state characterized by disorientation, inattention, confusion usually related to a metabolic condition -Most commonly associated with hospitalized patients aged 65 years and older - 20% 2/3 not treatred -Cognitive function fluctuates throughout the day -Wide range of symptoms and patient characteristics -Linked to poor clinical outcomes ◦ 1 year mortality rate of 35 - 40% Initiates a cascade of pathophysiological changes that lead to: ◦ Loss of independence ◦ Increased health care costs Yet, only 40% of health care workers routinely screen for delirium in at risk patients

Cholinergic Hypothesis of Delirium

Acetylcholine ◦ Memory & cognition Anticholinergic drugs cause delirium in healthy adults and the elderly population Patients with delirium show reduced brain cholinergic activity Dopamine (morphine/opitate inc dop.) Inhibitory effect on cholinergic activity ◦ Dopamine agonists induce delirium Dopamine antagonists treat some of the symptoms associated with delirium

Predisposing Factors : baseline

Coexisting Medical Conditions: illness, chronic renal,liver, smoking, neuro, HIV, terminal, fracture, severe ilness (3.4x) Sensory Impairment: visual - 3.5 x/hear Decreased Oral Intake: malnut/dehydration (3.5x) Cognitive Status:*dementia* and cognitive impair his of delirium/depression Primary Neurologic Diseases Functional Status: dependent, immobility and dec. activity, his fall Demographic characteristics: 65 &male : 75+ Drugs: psychomotor/ polypharamacy/alcohol abuse

Delirium & Dementia

Dementia is the leading predisposing risk factor for delirium Dementia and delirium are associated with decreased cerebral blood flow, cholinergic deficiency and inflammation 50% of delirium cases persist after discharge, from months to years Delirium worsens dementia and accelerates the patient's loss of independence May serve as an early warning sign of dementia

types of delirium

Hyperactive Hypoactive Mixed

Precipitating Factors: otherwise known as

NOXIOUS INSULTS from the hospitalization Drugs: sedative, narcotics, antichol, *multidrugs*, alcohol/drug abuse Primary Neurologic Diseases: stroke, brain bleeding, meningitis, enceph. Incurrent Illness: infectious, acute, hypoxia, shock, fever, hypoT, anemia, dehydration ,* decrease albumin * Surgery: othro, cardiac, Environmental: ICU, restraints(4.4x), catheter, pain,stress Prolonged Sleep Deprivation

Neuroinflammatory Hypothesis of Delirium -general

Provides an explanation as to how peripheral changes in the body may affect brain function and increase a patient's risk for developing delirium Offers insight as to why elderly patients are more vulnerable to delirium brain images show enlarged and damaged microglia in elderly non-delirious -cannot account fro all clinical features

Hyperactive -symptoms - what is it mistaken for?

Restlessness, constant movement, agitation insomnia, hyper vigilance, irritable, rapid speech ◦ May be mistaken for schizophrenia, bipolar disorder, or agitated dementia

Hypoactive -symptoms - what is it mistaken for?

Slowing or lack of movement, paucity of speech, unresponsiveness ◦ May be mistaken for depression ◦ Most common form of delirium ◦ Associated with a higher mortality, because improperly treated and diagnosed : 6m most common in elderly : 50%

Neuroinflammatory Hypothesis of Delirium - common conditions associated with delirium

Systemic inflammation conditions associated with delirium (medical and surgical condition) Delirium ◦ Clinical feature of sepsis, urinary tract infections, pneumonia, myocardial infarctions, fractures, etc... ◦ All of these conditions share a common thread Release and production of pro-inflammatory mediators into the systemic circulation Delirious patients have higher blood plasma levels of inflammatory cytokines than patients without delirium

Screening for Delirium

Use the Confusion Assessment Method Instrument (Y/n) -can used with incubated pt - have to have both acute onset and inattention WITH either disorganized thinking or change in LOC

what are the protective factors

age, cognitive, sensorial origins, status

why is it common to mix with schitz

because of hyper and hallucination BUT disorientation and fluctuation in LOC are rare in schitz, and diagnosis occurs in adolescent and with gradual onset proceeded by social isolation

Contributors to NT dysfunction; stressors metabolic dysfunction Electrolyte

cortisol,/hypoxia lactic acidosis hyperg/hypog IGF1 hypercapnia Na, Ca, Mg

Leading case in predisposing vs Precipitating -what classifies it as an increase risk?

dementia, cognitive, visual, his of alcohol, comorbidity, (stroke/depression) polypharamacy, psychoactive drugs, physical restraints, ann. labs 3 + risk factors = 60% inc

Neuroinflammatory Hypothesis of Delirium

neurons glia and astrocytes react to the presence of peripheral immune cells activation of the brain by peripheral immune cells leads to the production of cytokines, neuronal cell proliferation and activation of HPA axis, to allow CNS to help combat acute infections inc. perm. allow for infiltration of Blood-derived leukocytes and other inflammatory agents into the brain tissue in the brain these pro-inflammatory agents activates endothelial cells, microbial and astrocytes and induce morphical changes and initiates the productions of pro-inflammatory cytokines these changes causes the activity of adjacent endothelial cells, astrocytes and neurones impacting cerebral blood flow, signal propagation and neural excitability -causing the changes in neuroT and CBF = delirium

management of delirium

prevention and monitor LOC -change in LOC --CAM ---rule out other similar diseases (depression) ----confirm delirium -----supportive care and prevention complication --------protect airway/volume/ nutrition/skincare -----manage symptoms with non-pharm --------use pharm. if severe agitated (2-3days) ------identify predisposing factors --------review meds, labs, ECG, neuroimaging

Neuroinflammatory and neuroT dysregulation contributors : WHY?

stressors, metabolic derangement, electrolyte disorders and genetic factors -interfere with neural/cellular metabolism leading to acute cognition dysfunction

Mixed

◦ Alternating hyperactive and hypoactive states