This document discusses delirium in the ICU. It begins by defining delirium and describing its fluctuating nature and symptoms. Delirium is then categorized as hyperactive, hypoactive, or mixed. The document explains that delirium increases risks such as longer hospital stays, higher mortality, and long-term cognitive issues. It identifies risk factors and potential causes related to neurotransmitters, predispositions, and precipitants. Methods for diagnosing and monitoring delirium like the ICDSC and CAM-ICU are outlined. Finally, the document reviews treatments including non-pharmacological interventions and pharmacological options like haloperidol and atypical antipsychotics.

1. Delirium in the ICUDelirium in the ICU
from witness to criminalfrom witness to criminal
Dr. Andrew Ferguson
MEd FRCA FCARCSI DIBICM FCCP

2. ““The subject of delirium is generally looked upon by theThe subject of delirium is generally looked upon by the
practical physician as one of the most obscure in the chain ofpractical physician as one of the most obscure in the chain of
morbid phenomena he has to deal with; whilst the frequencymorbid phenomena he has to deal with; whilst the frequency
of its occurrence under various conditions of the systemof its occurrence under various conditions of the system
renders the affection not a little familiar to his eye”renders the affection not a little familiar to his eye”
Gallway MB (1838). Nature and treatment of delirium. Lond Med Gazette 1: 46–49.

3. OverviewOverview
What isWhat is deliriumdelirium??
How is it categorised?How is it categorised?
Why does it matter?Why does it matter?
Why does it happen?Why does it happen?
How do we diagnose/monitor it?How do we diagnose/monitor it?
How do we prevent and treat it?How do we prevent and treat it?
What does it mean for our patients?What does it mean for our patients?

4. What is Delirium?What is Delirium?
AnAn acuteacute confusional stateconfusional state withwith
FluctuatingFluctuating mental statusmental status
DisorderedDisordered attentionattention
DisorganisedDisorganised thinkingthinking OR alteredOR altered consciousnessconsciousness
DSM IV definitionDSM IV definition: “a disturbance of consciousness with: “a disturbance of consciousness with
inattention accompanied by a change in cognition or perceptualinattention accompanied by a change in cognition or perceptual
disturbance that develops over a short period (hours to days) anddisturbance that develops over a short period (hours to days) and
fluctuates with time”fluctuates with time”
SynonymsSynonyms: ICU psychosis, septic encephalopathy, ICU: ICU psychosis, septic encephalopathy, ICU
syndrome, acute brain failure, acute confusional statesyndrome, acute brain failure, acute confusional state

5. How is Delirium Categorised?How is Delirium Categorised?
HyperactiveHyperactive
HypoactiveHypoactive
MixedMixed
1.6% of cases, “ICU psychosis”, agitation,
restlessness, “picking”, emotional lability
1.6% of cases, “ICU psychosis”, agitation,
restlessness, “picking”, emotional lability
54.1% % of cases54.1% % of cases
43.5% of cases, “encephalopathy”, often
unrecognised, withdrawal, flat affect, apathy,
lethargy, decreased responsiveness, may be
misdiagnosed as depression
43.5% of cases, “encephalopathy”, often
unrecognised, withdrawal, flat affect, apathy,
lethargy, decreased responsiveness, may be
misdiagnosed as depression

6. Why does delirium matter?Why does delirium matter?
IncreasedIncreased reintubationreintubation risk (OR=3)risk (OR=3)
IncreasedIncreased ICU & hospital stayICU & hospital stay** (up to 10 days extra)(up to 10 days extra)
Each day in delirium increases risk of longer stay by 20%Each day in delirium increases risk of longer stay by 20%
Increased mortality in ICU & out to 6 months** (OR=3)Increased mortality in ICU & out to 6 months** (OR=3)
Each day spent in delirium increases risk of death by 10%Each day spent in delirium increases risk of death by 10%
IncreasedIncreased ICU & hospital costsICU & hospital costs******
10-24% risk of10-24% risk of long-term cognitive impairmentlong-term cognitive impairment
IncreasedIncreased dementia riskdementia risk
Reduced functional statusReduced functional status at 3 & 6 monthsat 3 & 6 months
* Ely et al, Intensive Care Med 2001; 27: 1892-1900 ** Ely et al, JAMA 2004; 291: 1753-62 *** Milbrandt et al, CCM 2004; 32: 955-62

8. Why does delirium happen?Why does delirium happen?
Higher cortical dysfunctionHigher cortical dysfunction (on functional neuroimaging)(on functional neuroimaging)
Pre-frontal cortex, non-dominant posterior parietal regions,Pre-frontal cortex, non-dominant posterior parietal regions,
anterior thalamus, basal ganglia, temporal-occipital cortexanterior thalamus, basal ganglia, temporal-occipital cortex
Neurotransmitter dysfunctionNeurotransmitter dysfunction
Reduced acetylcholine levels – blockade or deficiency
Endogenous anticholinergic substances
Opiates/hypoxia/inflammation
Serotonin fluctuationSerotonin fluctuation
Dopamine excessDopamine excess
Glutamate excess (2Glutamate excess (2oo
to IFN-to IFN-γγ, LPS, hypoxia, hypoglycaemia), LPS, hypoxia, hypoglycaemia)
Predisposition (baseline vulnerability)Predisposition (baseline vulnerability)
Precipitants (clinical, iatrogenic, organisational risk factors)Precipitants (clinical, iatrogenic, organisational risk factors)

9. Why does delirium happen?Why does delirium happen?
Serotonin
Acetylcholine
Dopamine
Serotonin
Acetylcholine
Dopamine
Opioids & benzo’sOpioids & benzo’s
2o
brain infection2o
brain infection
Decreased cerebral
metabolism
Decreased cerebral
metabolism
1o
intracranial
disease
1o
intracranial
disease
Systemic diseaseSystemic disease
HypoxiaHypoxia
Metabolic
derangement
Metabolic
derangement
Withdrawal
syndromes
Withdrawal
syndromes
ToxinsToxins

10. Risk factors for deliriumRisk factors for delirium
Van Rompaey Intensive and Critical Care Nursing 2008; 24: 98—107

11. AgeAge
SeveritySeverity
Benzo’sBenzo’sPun & Ely, Chest 2007; 132: 624–636
Pandharipande et al, Anesthesiology 2006; 104: 21-26

12. DELIRIUM(S) - causesDELIRIUM(S) - causes
DD Drugs, dementiaDrugs, dementia
EE Eyes & ears (poor vision and hearing)Eyes & ears (poor vision and hearing)
LL Low OLow O22 states (CHF, COPD, ARDS, MI, PE)states (CHF, COPD, ARDS, MI, PE)
II InfectionInfection
RR Retention (urine and stool)Retention (urine and stool)
II Ictal statesIctal states
UU Underhydration/undernutritionUnderhydration/undernutrition
MM Metabolic upsetMetabolic upset
(S)(S) Subdural, sleep deprivationSubdural, sleep deprivation

13. I WATCH DEATHI WATCH DEATH
II InfectionInfection
WW Withdrawal (alcohol, sedatives, barbiturates etc.)Withdrawal (alcohol, sedatives, barbiturates etc.)
AA Acute metabolic (acidosis, alkalosis, electrolytes)Acute metabolic (acidosis, alkalosis, electrolytes)
TT Trauma (closed head injury, haematoma etc.)Trauma (closed head injury, haematoma etc.)
CC CNS pathology (seizures, stroke, encephalitis)CNS pathology (seizures, stroke, encephalitis)
HH HypoxiaHypoxia
DD Deficiencies (thiamine, niacin, B12, folate)Deficiencies (thiamine, niacin, B12, folate)
EE Endocrinopathies (thyroid, glucose, adrenal)Endocrinopathies (thyroid, glucose, adrenal)
AA Acute vascular (hypertensive crisis, arrhythmia)Acute vascular (hypertensive crisis, arrhythmia)
TT Toxins/drugsToxins/drugs
HH Heavy metalsHeavy metals

14. Diagnosis & monitoringDiagnosis & monitoring
LevelLevel of consciousnessLevelLevel of consciousness
ContentContent of consciousnessContentContent of consciousness

15. Diagnosis & monitoringDiagnosis & monitoring
• Intensive Care Delirium Screening Checklist (ICDSC)
– 8 items based on data from preceeding 24 hours8 items based on data from preceeding 24 hours
– ScoreScore >> 4 items = positive for delirium4 items = positive for delirium
– Sensitivity 99%, specificity 64%, inter-observer reliability 94%Sensitivity 99%, specificity 64%, inter-observer reliability 94%
– SimpleSimple
• Confusion Assessment Method for ICU (CAM-ICU)
– 4 features4 features
1.1. Altered or fluctuating mental status compared to baselineAltered or fluctuating mental status compared to baseline
2.2. Inattention (Attention Screening Examination – ASE, visual or auditoryInattention (Attention Screening Examination – ASE, visual or auditory
recollection of letter or images)recollection of letter or images)
3.3. Disorganised thinking – 4 Y/N questions + hold up 2 fingers on each handDisorganised thinking – 4 Y/N questions + hold up 2 fingers on each hand
4.4. Altered consciousness – sedation scale e.g. RASSAltered consciousness – sedation scale e.g. RASS
– Delirium = 1 AND 2 plus 3 OR 4Delirium = 1 AND 2 plus 3 OR 4

18. ICDSCICDSC

19. CAM-ICUCAM-ICU

20. Treating deliriumTreating delirium
• Non-pharmacologicalNon-pharmacological (most studied outside ICU)(most studied outside ICU)
– Up to 40% risk reduction achievedUp to 40% risk reduction achieved
– Repeated reorientation of patientsRepeated reorientation of patients
– Early mobilisationEarly mobilisation
– Visual and hearing aids (and wax removal!)Visual and hearing aids (and wax removal!)
– Early catheter, line etc. removalEarly catheter, line etc. removal
– Minimise restraints and sedativesMinimise restraints and sedatives

21. Treating delirium -Treating delirium - haloperidolhaloperidol
– TypicalTypical antipsychoticantipsychotic
– 2-5 mg iv/po q6H (reduce in elderly)2-5 mg iv/po q6H (reduce in elderly)
– Adverse effectsAdverse effects – extrapyramidal, prolonged– extrapyramidal, prolonged
QTc, torsades (3.8%), neuroleptic malignantQTc, torsades (3.8%), neuroleptic malignant
syndromesyndrome
– More effective than lorazepamMore effective than lorazepam
– ? mortality reduction in ventilated ICU patients? mortality reduction in ventilated ICU patients
– Dopamine blockade + disinhibition of AChDopamine blockade + disinhibition of ACh
– Anti-inflammatory effectsAnti-inflammatory effects
Girard & Ely, Handbook of Clinical Neurology 2008; 90: chapter 3

22. Treating delirium – atypicalTreating delirium – atypical
antipsychoticsantipsychotics
– Olanzepine, quetiapine, risperidoneOlanzepine, quetiapine, risperidone
– Alter multiple neurotransmittersAlter multiple neurotransmitters includingincluding
DA, NA, serotonin, ACh, histamineDA, NA, serotonin, ACh, histamine
– Suggestion of decreased extrapyramidalSuggestion of decreased extrapyramidal
side-effects compared to haloperidolside-effects compared to haloperidol
– As effective as haloperidolAs effective as haloperidol
Girard & Ely, Handbook of Clinical Neurology 2008; 90: chapter 3
Skrobik YK, Bergeron N, Dumont M et al. (2004). Olanzapine vs haloperidol: treating delirium in a critical care set- ting. Intensive Care Med 30:
444–449.107: 341–351.
Han CS, Kim YK (2004). A double-blind trial of risperidone and haloperidol for the treatment of delirium. Psychosomatics 45: 297–301 Breitbart W,
Marotta R, Platt M et al. (1996). A double- blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized
AIDS patients. Am J Psychiatry 153: 231–237.

23. Internet ResourcesInternet Resources
www.icudelirium.orgwww.icudelirium.org