Delirium in critically ill

Should we worry?
Buddhika vidanagama
MBBS, MD,FRCA

Consultant Anaesthetist
National Cancer Institute Maharagama
 Delirium in critically ill
A serious acute medical condition
Effectively a medical emergency
Can result in serious adverse outcomes
Death and
Dementia
May be first sign of a new infection
Pathological not just psychological
 Delirium in critically ill
Most delirium goes undiagnosed
A quiet confusion
A brain failing by shut down
?brain dysfunction vs MODS

Can be diagnosed by a simple test

 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
Risk factors
Risk factors

Single most important

modifiable risk factor
in critical care is
the use of sedative drugs
 Risk factors
Host factors Acute illness Iatro/environ

Elderly Severe sepsis Sedative/analges

Co-morbidities ARDS Immobilisation
Pre-existing MODS TPN
cognitive impair
Hearing/vision Drug OD or Sleep
impairment illicit drugs deprivation
Neurological dis Nosocomial inf. Malnutrition
Alcohol/smoker Met. disturbance Anaemia
 Definition
Hippocrates described delirium as a fatal sign
Described agitated and lethargic variants.

An acute confusional state characterised by

fluctuating mental status
inattention, and
either disorganized thinking or altered level of
consciousness
 Definition
A clinical syndrome and a bedside diagnosis.
An acute change in mental status
Develops over short time, hours to days
Usually temporary
A fluctuating course worse at night
Always triggered by a precip. factor
Number one feature
An inability to maintain attention
 Delirium motoric types
Hyperactive (1%)
Psychomotor agitation
Hypoactive (34%)
Psychomotor lethargy and sedation
Appears quiet & co-operative BUT with
Inattention and disorganised thinking
Old age is a strong predictor
Mixed (65%)
Fluctuating hypo/hyperactive symptoms
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
 Delirium motoric types
Hypoactive
Associated with worse outcomes
Not depression, lack of motivation or a benign
residual drug effect it is delirium
To detect - need to screen for it
 Its all delirium
ICU psychosis
ICU syndrome
Acute confusional state
Acute brain failure
Septic encephalopathy
Acute brain dysfunction
Sun downing
 Diagnosing delirium

Neurological monitoring
Level of sedation
Drugs are given with specific agreed target of effect

2 validated screening tools to detect delirium in

critically ill patients
CAM-ICU - a confusion assessment method for
Intensive Care
ICDSC - Intensive Care Delirium Screening Checklist.
 Delirium screening
CAM-ICU 4 features

Needs 3 out of 4
Sensitivity/specificity - 95%
V. high inter-rater reliability
Ely et al CCM;29:1370-1379, 2001, Ely et al JAMA;286:2703-2710, 2001

ICDSC 8 items
Over one shift. 4 or more = delirium
Ely JAMA 2001, Bergeron ICM 2001
 CAM ICU
The Assessment tool
Feature 1: Acute onset of mental
status changes, or Fluctuating
course.
AND

Feature 2: Inattention

AND

Feature 3: Disorganised OR Feature 4: Altered level

thinking of consciousness

Sedation level - at least eye-opening to voice with or without eye contact

 Treatment

Identify and treat the precipitating cause

Deliriogenic drugs should be reduced or
withdrawn whenever possible.
Use daily sedation targets and spontaneous
awakening trials if tolerated.
Biochemical, hypoxic and haemodynamic
derangements should be corrected
Screen for infection, identify or treat most likely
source.
 Deliriogenic Drugs
Most easily reversible trigger factor
Most common are benzodiazepines,
anticholinergics & high dose narcotics
Analgesics: Antiemetics:
Codeine Prochlorperazine
Fentanyl Benzodiazepines:
Morphine Midazolam
Pethidine Lorazepam
Antidepressants: Cardiovascular agents:
Amitryptyline Atenolol
Paroxetine Digoxin
Anticonvulsants: Dopamine
Phenytoin Lidocaine
Antihistamines: Corticosteroids
Chlorphenamine Furosemide
Promethazine Ranitidine
 Different drugs implicated in different studies

Benzodiazepines, esp. lorazepam

?related to dose
Anticholinergics
Morphine
Corticosteroids
Maybe propofol and fentanyl

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
 Treatment
Pharmacological interventions
Should be treated pharmacologically if
Persistent
Delays the patients progress e.g. extubation, mobilisation or
Hyperactive and distressing.

Haloperidol
The drug of choice in all available guidelines
Only antipsychotic given i.v.

Alternative antipsychotics
Olanzapine
Risperidone & Quetiapine - limited evidence for use and safety,

Benzodiazepines
Deliriogenic
Ideally should be reserved alcohol withdrawal or when patient or staff safety may be at risk.
 Haloperidol
1950 shortly after chlorpromazine
D2 blockade of mesolimbic pathways
Blockade in nigrostriatal pathway
Variable sedation
Fewer vasomotor, cardiac central effects
Torsade de Pointes (QTc), extrapyramidal
60% bioavailability
Metabolised by oxidative dealkylation
Various dose schedules
2.5mgs to 5mgs starting dose
 Prevention

Delirium bundle
Directed at the risk factors has been shown to decrease the incidence,
duration, length of hospitalization and mortality.
Not known if this translates to better longer-term outcomes
Makes good clinical sense.
Establish baseline cognitive function from family/friends.
Improved psychotropic medication use.
Organization of nursing care to promote continuity of care and personal
knowledge.
Provide visual and hearing aids.
Reorientate patient verbally and visually - clock/calendar.
Attention to causes of sleep deprivation.
Mobilize early.
Ensure adequate pain control.
Avoid physical restraints.
Avoid constipation.
 Why it matters: Incidence
Commonest neuropsychiatric condition in
hospitalised patients
l5% to 25% on general medical ward
Up to 60% on surgical wards
Critical care - up to 80% in the sickest ventilated
patient
Onset: ICU day 2 (+/- 1.7)
How long: 4.2 (+/- 1.7) days
 Why it matters: Incidence
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
 Why it matters: Outcomes

Death
An independent predictor of death in intensive care
patients
After adjusting for age, gender, race, pre-existing comorbidity &
cog impairment, ICU diagnosis and severity of illness
3 times more likely to die at 6 months
Each additional day spent in delirium is associated with a
20% increased risk of prolonged hospitalization
10% increased risk of death.
Predictive of a 3-fold higher reintubation rate
Over 10 additional days in the hospital
financial and human costs
 Why it matters: Outcomes
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
 Why it matters: Outcomes
Dementia
Emerging data
Delirium may lead to or accelerate dementia
Relationship between delirium and long-term
cognitive outcomes
Consistently demonstrated a link
One third of ventilated
Long-term cognitive impairment persisting at 3 years.
 Why it matters: Outcomes
Dementia & delirium
203 patients, 38 with delirium 22 with dementia,
16 without. 32 month follow up.
Incidence of dementia - 18.1% per year with
delirium, 5.6% without

Rockwood et al, Age and aging 1999;28:551-556

 Why it matters: Outcomes
Prolonged ICU/hospital stays
1.6 fold increase in ICU costs
Institutionalisation
 Why it matters: Outcomes
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
 Why it matters:
Impact on post op patients
Incidence of POD was 13.2 % (17.9 % for em ops).
Independent associated variables: age > 75 years, co-
morbidity, preop cognitive imp, psychopathological
symptoms & abnormal glycaemic control. Median LOS 21
(1-75) days for POD vs 8 (1-79) days for control (P <
0.001). Hospital mortality rate 19 & 8.4 % respectively (P
= 0.021).

Risk factors and incidence of postoperative delirium in elderly patients after

elective and emergency surgery. Ansaloni L, Catena F, Chattat R, Fortuna D,
Franceschi C, Mascitti P, Melotti RM. Br J Surg. 2010 Feb;97(2):273-80.
 Why it matters:
Impact on post op patients

A fast-track set-up with multimodal opioid-

sparing analgesia was associated with lack of POD
after elective THA and TKA in elderly patients.

Delirium after fast-track hip and knee arthroplasty L.

Krenk, L. S. Rasmussen, T. B. Hansen, S. Bog,K.
Sballe,H. Kehlet. BJA 2012 Volume 108, Issue 4, Pp.
607-611
 Why it matters: Outcomes
After leaving ITU, patient is unable to return to
anything like the life they enjoyed before

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 peoples
names that I have worked with for years. I cant
remember where I put things at home. I cant help my
children with their homework because I cant
remember how to do simple multiplication problems.
 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 contributing to MOF.
Bergeron Critical Care 2005;9:R375-381
 Conclusion
Delirium in critically ill should we worry?

Yes !!
Increases mortality, duration of ICU & hospital stay &
health costs
Cause dementia & long term impairment of cognitive
functions
May be preventable
Treatable
Needs to be diagnosed first
You will find it

Only If you look for it

Thank you