Delirium in critical illness
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 BUT
with 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 delirium
Longer ventilation & ITU stay – 4 days
Midazolam use strongest modifiable predictor
Pandiharipande 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
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 or
damage by metabolic/inflammatory
mediators
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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, Marcantonio
JAMA 1994 Tune Lancet 1981, Mussi J Geriatri Psych Neurol 1999, Marcantonio J Geront A Biol Sci Med Sci 20
Goyette Semin Resp CCM 2004, Sharshar ICM 2007
Delirium is often invisible
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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
Risk factors
Host factors
Acute illness
Iatro/environ
Elderly
Severe sepsis
Sedative/analges
Co-morbidities
ARDS
Immobilisation
Pre-existing
cognitive impair
Hearing/vision
impairment
Neurological dis
MODS
TPN
Drug OD or
Sleep
illicit drugs
deprivation
Nosocomial inf. Malnutrition
Alcohol/smoker Met. disturbance Anaemia
Precipitating factors
INFECTION
 Hyponatraemia
 Temperature
 Maintenance of arterial pressure
 Glucose
 Benzodiazepines
 Hypoxia, hypercarbia
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Vaquero et al. Sem in Liver Dis. 2003;32:59-69
Medications cause delirium
Different drugs implicated in different studies
 Benzodiazepines, esp. lorazepam
?related to dose
 Corticosteroids
 Morphine
 Maybe propofol and fentanyl
 Anticholinergics
Pandharipande 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
Does it matter?
After adjusting for age, gender, race, pre-existing
comorbidity & cog impairment, ICU diagnosis
and 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
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
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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
Delirium and death
In 275 medical ITU patients
Independent predictor 6 month mortality:
34% with delirium v. 15% without p=0.03
After adjusting for covariates
Hazard ratio death: 3.2 (CI 1.4 – 7.7)
203 general medical patients
Adj. relative mortality risk 1.8
Median survival 510 days v. 1122 days
Rockwood Age & Aging 1999;28(6):551-6, Ely et al JAMA 2004;291:1753-1762
Dementia after delirium
203 patients, 38 with delirium – 22 with
dementia, 16 without. 32 month follow up.
Incidence of dementia 5.6% per year without
delirium, 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
Medical ITU patients
11 of 34 patients neuropsychologically
impaired.
 Generally diffuse but primarily areas of
psychomotor speed, visual & working
memory, verbal fluency and visuoconstruction.
 Clinically significant depression in 36%
these patients.
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Jackson CCM 2005;31(4):1226-1234
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 simple
multiplication 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
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
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.
AND
Feature 2: Inattention
AND
Feature 3: Disorganised
thinking
OR
Feature 4: Altered level of
consciousness
CAM-ICU
Sedation level at least eye-opening to voice with or
without eye contact.
Feature 1: is patient different from baseline?
Or: any fluctuations in mental status 24/12?
Feature 2: looking for inattention – ASE letters, if
unclear status – ASE pictures using hand squeeze.
If both positive:
Feature 3: Disorganised thinking, a) 4 questions – 2
or more incorrect responses is positive. b) Holding
up fingers.
Feature 4: Altered conscious level i.e. drowsy +
Management:
treat cause(s) & reduce risks
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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
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Inouye. NEJM 1999;340(9):669
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Management
Pharmacological therapy
Antipsychotics:
Haloperidol: dopamine receptor
antagonist D2, variable sedation
side effects: torsades de pointes (QTc)
extrapyramidal.
Newer atypicals: Olanzepine, Quetiapine
Benzodiazepines:
Deliriogenic, alcohol withdrawal.
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 of
cytokines, cell infiltration & tissue damage.
 CNS immune activation accompanied by
peripheral production of TNF, interleukin 1
& interferon δ contributing to MOF.
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Bergeron Critical Care 2005;9:R375-381
www.icudelirium.co.uk
www.icudelirium.org
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