An acute medical condition. Common in UK critical care patients. Serious adverse outcomes. Bedside diagnosis. Maybe the first sign of a new infection. Pathological, not psychological.

1. Delirium in critical illness
Presented by
Khaled Mahmoud Azab Mohamed
Emergency medicine registrar
Aseer Central Hospital
2010

2. 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

3. 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

4. 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

5. “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

6. 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
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

7. 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

8. 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

9. Precipitating factors
 INFECTION
 Hyponatraemia
 Temperature
 Maintenance of arterial pressure
 Glucose
 Benzodiazepines
 Hypoxia, hypercarbia
Vaquero et al. Sem in Liver Dis. 2003;32:59-69

10. 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

11. 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

12. 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

13. 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

14. 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

15. Medical ITU patients
 11 of 34 patients neuropsychologically
impaired.
 Generally diffuse but primarily areas of
psychomotor speed, visual & working
memory, verbal fluency and visuo-
construction.
 Clinically significant depression in 36%
these patients.
Jackson CCM 2005;31(4):1226-1234

16. 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.”

17. 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

18. 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

19. 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.

20. The Assessment tool!
Feature 1: Acute onset of mental status
changes, or Fluctuating course.
Feature 2: Inattention
AND
AND
Feature 3: Disorganised
thinking
Feature 4: Altered level of
consciousness
OR

21. 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 +

22. 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

23. 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.

24. 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

25. 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.
Bergeron Critical Care 2005;9:R375-381