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Delirium
An overview
Pre test
•
A)
B)
C)
D)
E)
If you have 100 patients aged 65 and
older in a hospital, how many- at any
given time-will be delirious?
5
10
20
50
80
•
A)
B)
C)
D)
Delirium is reversible:
sometimes.
Always.
Never.
Sometimes, and to a variable degree.
• Delirium in older people is:
A) Inevitable.
B) Preventable, but through very costly and
complicated measures.
C) Very simple measures can prevent many
cases.
•
•
•
•
•
•
Definition
Burden
Classification
Pathophysiology
Clinical features
Diagnosis
• Complications
• Prognosis
• Prevention …
Delirium
• An acute, fluctuating disturbance of
consciousness, associated with a change
in cognition or the development of
perceptual disturbances.
• It is the pathophysiologic consequence of
an underlying general medical condition
such as infection, coronary ischemia,
hypoxemia, or metabolic derangement.
Burden
•
•
Mortality rates among hospitalized patients
with delirium range from 22-76 %.
(just like acute MIs or sepsis!!)
One-year mortality rate 35-40 %.
Inouye SK. Delirium in older persons, review article. N Eng J Med 2006;
354:1157-65.
Burden
• 20 % of in patients 65 years of age or older.
• Increases hospital costs by $2,500(US) per
patient.
• Substantial additional costs accrue after
discharge (institutionalization, rehabilitation,
formal home health care, and informal
caregiving).
• Prevalence at hospital admission:14-24 %.
• Incidence during hospitalization: 6-56%.
Pathophysiology
• Poorly understood.
• EEG: diffuse slowing of cortical background
activity, which does not correlate with underlying
causes.
• Neuropsychological and neuroimaging studies
reveal generalized disruption in higher cortical
function, with dysfunction in the prefrontal
cortex, subcortical structures, thalamus, basal
ganglia, frontal and temporoparietal cortex,
fusiform cortex, and lingual gyri, particularly on
the nondominant side.
Cholinergic deficiency
• The leading hypotheses for the pathogenesis of delirium
focus on the roles of neurotransmission, inflammation,
and chronic stress.
• Extensive evidence supports the role of cholinergic
deficiency.
• Anticholinergic drugs induce delirium in humans and
animals.
• Serum anticholinergic activity is increased.
• Physostigmine reverses delirium associated with
anticholinergic drugs, and cholinesterase inhibitors
appear to have some benefit even in cases of delirium
that are not induced by drugs.
Dopamine
• Dopaminergic excess also appears to
contribute.
• Possibly owing to its regulatory influence
on the release of acetylcholine.
• Dopaminergic drugs (e.g., levodopa and
bupropion) are recognized precipitants of
delirium, and dopamine antagonists (e.g.,
antipsychotic agents) effectively treat
delirium symptoms.
Other neurotransmitters
•
•
•
•
•
Norepinephrine.
Serotonin.
Aminobutyric acid
Glutamate.
Melatonin.
1.Lewis M, Barnett S. post operative delirium: the tryptophan dyregulation model
2.Medical hypotheses (2004) 63, 402-406
Others
• Cytokines(IL-1,2,&6), TNF, and interferon, may
contribute increasing the permeability of the
blood–brain barrier and altering
neurotransmission.
• Chronic stress brought on by illness or trauma
activates the sympathetic nervous system and
hypothalamic–pituitary–adrenocortical axis,
resulting in increased cytokine levels and
chronic hypercortisolism.
• Chronic hypercortisolism has deleterious effects
on hippocampal serotonin 5-HT1A receptors.
Risk factors
• Cognitive impairment:
• 25% of delirious patients are demented
• 40% of demented hospitalized are
delirious.
• Five independent risk factors for delirium at
discharge were identified:
• Dementia (OR: 2.3; 95% CI, 1.4-3.7).
• Vision impairment (OR, 2.1; 95% CI, 1.3-3.2).
• Functional impairment (OR, 1.7; 95% CI, 1.23.0).
• High comorbidity (OR, 1.7; 95% CI, 1.1-2.6).
• Use of physical restraints during delirium (OR,
3.2; 95% CI, 1.9-5.2).
Risk Factors for Delirium at Discharge . Development and Validation of a
Predictive Model
Inouye et al.,Arch Intern Med. 2007;167:1406-1413
• A risk stratification system was created by
adding 1 point for each factor present.
• Risk of delirium on discharge:
• Low-risk (0-1 factors):
4%
• Intermediate-risk (2-3 factors):
18%
• High-risk (4-5 factors):
63%.
(P < .001).
Peri operative delirium
• The incidence of delirium : 5.1%-52.2%.
• Greater rates after hip fracture and aortic surgeries.
• Risk factors:
cognitive impairment, older age, functional
impairment, sensory impairment, depression,
preoperative psychotropic drug use, psychopathological
symptoms, institutional residence, and greater
comorbidity.
• Evidence was most robust for an association between
delirium and cognitive impairment or psychotropic drug
use.
Preoperative Risk Assessment for Delirium After Noncardiac Surgery: A Systematic Review
M Dasgupta, C. Dumbrell, JAGS, Volume 54, Issue 10: 1578-1589
Clinical Features
• Hyperactive: an increased state of arousal,
psychomotor abnormalities, and hypervigilance.
• Hypoactive: withdrawn, less active, and sleepy.
• Maybe misdiagnosed as dementia or
depression.
• Poorer overall prognosis.
• Mixed..
• Delirium often is the presenting symptom of an
underlying illness
DSM-IV Criteria
– Disturbance of consciousness (ie, reduced clarity of awareness
of the environment), with reduced ability to focus, sustain, or shift
attention.
– Change in cognition (eg, memory deficit, disorientation,
language disturbance, perceptual disturbance) that is not better
accounted for by a preexisting, established, or evolving
dementia.
– The disturbance develops over a short period ( hours to days)
and tends to fluctuate during the course of the day.
– Evidence from the history, physical , or laboratory findings is
present that indicates the disturbance is caused by a direct
physiologic consequence of a general medical condition, an
intoxicating substance, medication use, or more than one cause
CAM (Confusion assessment method)
Sn 94-100% Sp 90-95%.
• 1: Acute Onset and Fluctuating Course
Usually obtained from a family member or nurse.
Is there evidence of an acute change in mental
status from the patient's baseline? Did the
(abnormal) behavior fluctuate during the day,
that is, tend to come and go, or increase and
decrease in severity?
• 2: Inattention
Did the patient have difficulty focusing attention,
ie. easily distractible, or having difficulty keeping
track of what was being said?
• 3: Disorganized thinking
Was the patient's thinking disorganized or incoherent?
( rambling or irrelevant conversation, unclear or illogical
flow of ideas, or unpredictable switching from subject to
subject)
• 4: Altered Level of consciousness
Any answer other than "alert" to the following question::
Overall, how would you rate this patient's level of
consciousness? (alert, vigilant, lethargic, stupor, or
coma)
• The diagnosis requires 1 and 2 and either 3 or 4.
Other instruments
• DRS (Delirium rating scale).
• MDAS (Memorial delirium assessment
scale).
• DSI (Delirium symptom interview).
• CTD (cognitive test for delirium).
• Features
•
•
•
•
•
•
•
Delirium
Onset
Acute
Course
Fluctuating
Duration
Days to weeks
Consciousness
Altered
Attention
Impaired
Psychomotor
↑ or ↓
Reversibility
Usually
Dementia
Insidious
Progressive
Months to yrs
Clear
Normal
Often normal
Rarely
Prognosis
Prognosis
• Persists in up to 25% of patients.
• When is it not delirium anymore??
• Higher in-hospital and post discharge
mortality.
• Longer lengths of stay.
• Functional decline – placement.
Complications
• Immobility and it’s complications:
( aspiration, thromboembolism, UTI,
pressure ulcers)
• Underlying cause.
Prevention
• Non pharmacological:
Multicomponent Intervention to Prevent Delirium in Hospitalized
OlderPatients
Inouye SK, et al.
N Engl J Med 340:669, March 4, 1999
Pharmacological
Haloperidol:
• RCT of 430 patients, 70 y and older.
• Hip replacement surgery.
• Haloperidol 1.5 mg preop and 3 days post.
• Positive effect on the LOS, severity and
duration of delirium, but not the incidence.
• Well tolerated.
Kalisvaar KJ, et al .Haloperidol prophylaxis for elderly hip-surgery
patients at risk for delirium: a randomized placebo-controlled study.
J Am Geriatr Soc. 2005 Oct;53(10):1658-66
•
•
•
Melatonin:
Treated severe postoperative delirium
unresponsive to antipsychotics or benzos
in a 53y patient.
prevented another episode of postop.
delirium in a 78y patient with a prior
history of postoperative delirium, after
undergoing repeated LL surgery.
Hanania m, Kitain E. Melatonin for treatment and prevention of
postoperative delirium. Anasth Analg 2002;94:338-9