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Delirium in critical illness
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Delirium
An acute medical condition
Common in UK critical care patients
Serious adverse outcomes
Bedside diagnosis
May be first sign of a new infection
Pathological not psychological
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Delirium
Disturbance of consciousness
Acute change in mental status
Fluctuating course – worse at night
Develops over short time, hours to days
Impaired attention
Disorganised thinking
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Delirium motoric types
Hyperactive – psychomotor agitation
Hypoactive – psychomotor lethargy and
sedation, appears quiet & co-operative BUTwith inattention and disorganised thinking.
Mixed – fluctuating hypo/hyperactive
symptoms
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“Acute brain dysfunction”
Prevalence of up to 80% quoted in ITU
100 ITU surgical patients:
69% with deliriumLonger ventilation & ITU stay – 4 days
Midazolam use strongest modifiable predictorPandiharipande et al. 2006 SCCM
118 ITU medical patients over 65:31% on admission.
70% during hospitalisation
McNicoll J AM Geriatri Soc. 2003;51(5):591
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Pathophysiology
Neuroimaging – 42% ↓CBF, atrophy
Psychoactive drugs 3-11 fold ↑RR delirium
Related to surgery – multifactorial
Biomarkers – serum anticholinergic activity Neurotransmitters – imbalance in all
monoamines, GABA, glutamate and Ach
Sepsis: blood brain barrier breakdown ordamage by metabolic/inflammatorymediators
Yokota. Psych.Clin.Neurosci 2003, Fong. J Geront A Biol Sci Med Sci 2006, Koponen J Nerv Ment Dis 1989,Hopkins Brain Inj 2006, Chang R Neurosig 2006 Inoyue Am J Med 1999, Pandharipande Anesth 2006, MarcantonioJAMA 1994 Tune Lancet 1981, Mussi J Geriatri Psych Neurol 1999, Marcantonio J Geront A Biol Sci Med Sci 20Goyette Semin Resp CCM 2004, Sharshar ICM 2007
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Delirium is often invisible
The vast majority of delirium in ICU is either
hypoactive “quiet” subtype (35%) or mixed (64%)
Very little (1%) is the pure hyperactive subtype. Older age is a strong predictor of hypoactive
delirium
Hypoactive delirium has worse outcomes
Onset: ICU day 2 (+/- 1.7)
How long: 4.2 (+/- 1.7) days Ely et al JAMA 2001;286:2703-2710 Ely et al CCM 2001;9:1370-1379
Peterson et al JAGS 2006 in press McNicholl JAGS 2003;51:591-598
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Risk factors
Host factors Acute illness Iatro/environ
Elderly Severe sepsis Sedative/analges
Co-morbidities ARDS Immobilisation
Pre-existing
cognitive impair
MODS TPN
Hearing/vision
impairment
Drug OD or
illicit drugs
Sleep
deprivation
Neurological dis Nosocomial inf. Malnutrition
Alcohol/smoker Met. disturbance Anaemia
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Precipitating factors
INFECTION
Hyponatraemia
Temperature
Maintenance of arterial pressure
Glucose
Benzodiazepines Hypoxia, hypercarbiaVaquero et al. Sem in Liver Dis. 2003;32:59-69
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Medications cause delirium
Different drugs implicated in different studies
Benzodiazepines, esp. lorazepam
?related to dose Corticosteroids
Morphine
Maybe propofol and fentanyl AnticholinergicsPandharipande et al. Anesth;104(1):21-26,2006Dubois ICM 2001;27:1297-1304,
Marcantonio. JAMA, 1994;272:1518-1522, Gadreau J of Clin Onc. 23(27):6712-6718
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Does it matter?After adjusting for age, gender, race, pre-existing
comorbidity & cog impairment, ICU diagnosisand severity of illness
3 fold higher rate of death by 6 months 1.6 fold increase in ICU costs.
Longer hospital stays
Nearly 10x rate cognitive impairment on
discharge. 1 in 3 survivors with delirium develop cognitive
impairment.
Institutionalisation
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Does it matter?
Increased ICU LOS 8 vs. 5 days
Increased Hosp. LOS 21 vs. 11 days
Increased time on vent 9 vs. 4 days
Higher costs $22 000 vs. $13 000
3 fold increased risk of death
Poss. incrd longterm cognitive impairment Ely ICM 2001;27,1892-1900, Ely JAMA 2004;291:1753-1762, Lim SM, CCM 2004;32:2254-2259,
Milbrandt E, CCM 2004;32:955-962, Jackson Neuropsychology Review 2004;14:87-98
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Delirium and death
In 275 medical ITU patients
Independent predictor 6 month mortality:
34% with delirium v. 15% without p=0.03After adjusting for covariates
Hazard ratio death: 3.2 (CI 1.4 – 7.7)
203 general medical patientsAdj. relative mortality risk 1.8
Median survival 510 days v. 1122 daysRockwood Age & Aging 1999;28(6):551-6, Ely et al JAMA 2004;291:1753-1762
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Dementia after delirium
203 patients, 38 with delirium – 22 with
dementia, 16 without. 32 month follow up.
Incidence of dementia 5.6% per year withoutdelirium, 18.1% with.
Relative risk of death adjusted incr 1.8 +
significantly shorter median survival time
Rockwood et al, Age and aging 1999;28:551-556
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Medical ITU patients
11 of 34 patients neuropsychologicallyimpaired.
Generally diffuse but primarily areas of psychomotor speed, visual & workingmemory, verbal fluency and visuo-construction.
Clinically significant depression in 36%these patients.
Jackson CCM 2005;31(4):1226-1234
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Delirium and outcome
40 year old ARDS ICU survivor college graduate
“I have been out of hospital and trying to get on with
my life for the past 2 years. I have trouble with people’s names that I have worked with for years.
I can’t remember where I put things at home. I
can’t help my children with their homework
because I can’t remember how to do simplemultiplication problems.”
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Neurological monitoring
Level of sedation.
Drugs are given with specific agreed
target of effect.Screen for delirium
Confusion assessment method for the ICU
CAM-ICU, sensitivity/specificity 95%V. high inter-rater reliability
Ely et al CCM;29:1370-1379, 2001, Ely et al JAMA;286:2703-2710, 2001
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Delirium screening
CAM-ICU –
4 features
Altered mental status
Inattention; Indentify As in 10 letter spoken sequence
SAVE A HAART
Disorganised thinking
Altered level of consciousness
ICDSC – 8 items
Over one shift. 4 or more = delirium
Ely JAMA 2001, Bergeron ICM 2001
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CAM-ICU Incorporates 4 key features from
definition of delirium, 1 minute to do
1. Change in mental status from baseline or
fluctuating course.
2. Inattention
3. Disorganised thinking
4. Altered level of consciousness
Needs 1 & 2 with either 3 or 4.
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The Assessment tool!Feature 1: Acute onset of mental
status changes, or Fluctuating course.
Feature 2: Inattention
AND
AND
Feature 3: Disorganisedthinking
Feature 4: Altered level ofconsciousness
OR
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CAM-ICU
Sedation level at least eye-opening to voice with orwithout eye contact.
Feature 1: is patient different from baseline?
Or: any fluctuations in mental status 24/12?
Feature 2: looking for inattention – ASE letters, ifunclear status – ASE pictures using hand squeeze.
If both positive:
Feature 3: Disorganised thinking, a) 4 questions – 2or more incorrect responses is positive. b) Holdingup fingers.
Feature 4: Altered conscious level i.e. drowsy +
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Management:
treat cause(s) & reduce risks Treat underlying infection and CCF
Correct metabolic disturbance & hypoxia
Frequent reorientation of patient Goal directed sedation/analgesia &/or daily
wakeup.
Stop ventilator each day to test readiness
Early mobilisation
Attention to optimising sleep patterns Inouye. NEJM 1999;340(9):669
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Management
Pharmacological therapyAntipsychotics:
Haloperidol: dopamine receptor
antagonist D2, variable sedationside effects: torsades de pointes (QTc)
extrapyramidal.
Newer atypicals: Olanzepine, QuetiapineBenzodiazepines:
Deliriogenic, alcohol withdrawal.
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Haloperidol
1950 shortly after chlorpromazine
D2 blockade mesolimbic pathways
Blockade in nigrostriatal pathway – EPS
Fewer vasomotor, cardiac central effects
60% bioavailability
Metabolised by oxidative dealkylation
Various dose schedules
2.5mgs to 5mgs starting dose
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Delirium and Negative outcome
Cause-and-effect? Systemic infections & injury ► brain
dysfunction generation of CNS
inflammatory response ►Production ofcytokines, cell infiltration & tissue damage.
CNS immune activation accompanied by
peripheral production of TNF, interleukin 1& interferon δ contributing to MOF.
Bergeron Critical Care 2005;9:R375-381
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