Delirium in critical illness
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
Disturbance of consciousness
 Acute change in mental status
 Fluctuating course – worse at night
 Develops over short time, hours to days
 Impaired attention
 Disorganised thinking
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
“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
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
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
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
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
Severe sepsis
cognitive impair
Neurological dis
Drug OD or
illicit drugs
Nosocomial inf. Malnutrition
Alcohol/smoker Met. disturbance Anaemia
Precipitating factors
 Hyponatraemia
 Temperature
 Maintenance of arterial pressure
 Glucose
 Benzodiazepines
 Hypoxia, hypercarbia
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
 1 in 3 survivors with delirium develop cognitive
 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
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
 Generally diffuse but primarily areas of
psychomotor speed, visual & working
memory, verbal fluency and visuoconstruction.
 Clinically significant depression in 36%
these patients.
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.”
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
Disorganised thinking
Altered level of consciousness
ICDSC – 8 items
Over one shift. 4 or more = delirium
Ely JAMA 2001, Bergeron ICM 2001
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.
The Assessment tool!
Feature 1: Acute onset of mental
status changes, or Fluctuating course.
Feature 2: Inattention
Feature 3: Disorganised
Feature 4: Altered level of
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 +
treat cause(s) & reduce risks
Treat underlying infection and CCF
Correct metabolic disturbance & hypoxia
Frequent reorientation of patient
Goal directed sedation/analgesia &/or daily
Stop ventilator each day to test readiness
Early mobilisation
Attention to optimising sleep patterns
Inouye. NEJM 1999;340(9):669
Pharmacological therapy
Haloperidol: dopamine receptor
antagonist D2, variable sedation
side effects: torsades de pointes (QTc)
Newer atypicals: Olanzepine, Quetiapine
Deliriogenic, alcohol withdrawal.
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
Delirium and Negative outcome
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.
Bergeron Critical Care 2005;9:R375-381

Delirium PowerPoint Presentation