Delirium in the ICUDelirium in the ICUfrom witness to criminalfrom witness to criminal

Dr. Andrew FergusonMEd FRCA FCARCSI DIBICM FCCP

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

OverviewOverviewWhat is What 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?

What is Delirium?What is Delirium?An An acuteacute confusional state confusional state withwith

FluctuatingFluctuating mental status mental statusDisordered Disordered attentionattentionDisorganised Disorganised thinkingthinking OR altered OR altered consciousnessconsciousness

DSM IV definitionDSM IV definition: “a disturbance of consciousness : “a disturbance of consciousness with inattention accompanied by a change in cognition with inattention accompanied by a change in cognition or perceptual disturbance that develops over a short or perceptual disturbance that develops over a short period (hours to days) and fluctuates with time”period (hours to days) and 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

How is Delirium How is Delirium Categorised?Categorised?

Hyperactive

Hypoactive

Mixed

1.6% of cases, “ICU psychosis”, agitation, restlessness, “picking”, emotional lability

54.1% % of cases

43.5% of cases, “encephalopathy”, often unrecognised, withdrawal, flat affect, apathy, lethargy, decreased responsiveness, may be misdiagnosed as depression

Why does delirium Why does delirium matter?matter?

Increased Increased reintubationreintubation risk (OR=3) risk (OR=3)Increased Increased 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%Increased Increased ICU & hospital costsICU & hospital costs******10-24% risk of 10-24% risk of long-term cognitive impairmentlong-term cognitive impairmentIncreased Increased dementia riskdementia riskReduced functional status Reduced 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

Why does delirium Why does delirium happen?happen?

Higher cortical dysfunction Higher 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 dysfunctionReduced acetylcholine levels – blockade or deficiency

Endogenous anticholinergic substancesOpiates/hypoxia/inflammation

Serotonin fluctuationSerotonin fluctuationDopamine excessDopamine excessGlutamate excess (2Glutamate excess (2oo to IFN- to IFN-, LPS, hypoxia, hypoglycaemia), LPS, hypoxia, hypoglycaemia)

Predisposition (baseline vulnerability)Predisposition (baseline vulnerability)Precipitants (clinical, iatrogenic, organisational risk factors)Precipitants (clinical, iatrogenic, organisational risk factors)

Why does delirium Why does delirium happen?happen?

SerotoninAcetylcholin

eDopamine

Opioids & benzo’s

2o brain infection

Decreased cerebral

metabolism

1o intracranial disease

Systemic disease

Hypoxia

Metabolic derangement

Withdrawal syndromes

Toxins

Risk factors for deliriumRisk factors for delirium

Van Rompaey Intensive and Critical Care Nursing 2008; 24: 98—107

Age

Severity

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

DELIRIUM(S) - causesDELIRIUM(S) - causesDD Drugs, dementiaDrugs, dementiaEE 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 Infection Infection RR Retention (urine and stool)Retention (urine and stool)II Ictal statesIctal statesUU Underhydration/undernutritionUnderhydration/undernutritionMM Metabolic upsetMetabolic upset(S)(S) Subdural, sleep deprivationSubdural, sleep deprivation

I WATCH DEATHI WATCH DEATHII InfectionInfectionWW Withdrawal (alcohol, sedatives, barbiturates Withdrawal (alcohol, sedatives, barbiturates etc.)etc.)AA Acute metabolic (acidosis, alkalosis, Acute metabolic (acidosis, alkalosis, electrolytes)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 HypoxiaHypoxiaDD Deficiencies (thiamine, niacin, B12, folate)Deficiencies (thiamine, niacin, B12, folate)EE Endocrinopathies (thyroid, glucose, adrenal)Endocrinopathies (thyroid, glucose, adrenal)AA Acute vascular (hypertensive crisis, Acute vascular (hypertensive crisis, arrhythmia)arrhythmia)TT Toxins/drugsToxins/drugsHH Heavy metalsHeavy metals

Diagnosis & monitoringDiagnosis & monitoring

LevelLevel of consciousness

ContentContent of consciousness

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– Score Score >> 4 items = positive for delirium 4 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 features1.1. Altered or fluctuating mental status compared to baselineAltered or fluctuating mental status compared to baseline2.2. Inattention (Attention Screening Examination – ASE, visual Inattention (Attention Screening Examination – ASE, visual

or auditory recollection of letter or images)or auditory recollection of letter or images)3.3. Disorganised thinking – 4 Y/N questions + hold up 2 Disorganised thinking – 4 Y/N questions + hold up 2

fingers on each handfingers on each hand4.4. Altered consciousness – sedation scale e.g. RASSAltered consciousness – sedation scale e.g. RASS– Delirium = 1 AND 2 plus 3 OR 4 Delirium = 1 AND 2 plus 3 OR 4

ICDSC

CAM-ICU

Treating deliriumTreating delirium• Non-pharmacological Non-pharmacological (most studied outside (most studied outside

ICU)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 Visual and hearing aids (and wax

removal!)removal!)– Early catheter, line etc. removalEarly catheter, line etc. removal– Minimise restraints and sedativesMinimise restraints and sedatives

Treating delirium - Treating delirium - haloperidolhaloperidol

– TypicalTypical antipsychotic antipsychotic– 2-5 mg iv/po q6H (reduce in elderly)2-5 mg iv/po q6H (reduce in elderly)– Adverse effects Adverse effects – extrapyramidal, – extrapyramidal,

prolonged QTc, torsades (3.8%), neuroleptic prolonged QTc, torsades (3.8%), neuroleptic malignant syndromemalignant syndrome

– More effective than lorazepamMore effective than lorazepam– ? mortality reduction in ventilated ICU ? mortality reduction in ventilated ICU

patientspatients– Dopamine blockade + disinhibition of AChDopamine blockade + disinhibition of ACh– Anti-inflammatory effectsAnti-inflammatory effects

Girard & Ely, Handbook of Clinical Neurology 2008; 90: chapter 3

Treating delirium – atypical Treating delirium – atypical antipsychoticsantipsychotics

– Olanzepine, quetiapine, risperidoneOlanzepine, quetiapine, risperidone– Alter multiple neurotransmitters Alter multiple neurotransmitters

including DA, NA, serotonin, ACh, including DA, NA, serotonin, ACh, histaminehistamine

– Suggestion of decreased Suggestion of decreased extrapyramidal side-effects extrapyramidal side-effects compared to haloperidolcompared to haloperidol

– As effective as haloperidolAs effective as haloperidolGirard & 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.

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