Delirium in critical illness

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

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

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

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

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

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

Risk factors
Host factors Elderly Co-morbidities Pre-existing cognitive impair Hearing/vision impairment Neurological dis Acute illness Severe sepsis ARDS MODS Iatro/environ Sedative/analges Immobilisation TPN

Drug OD or Sleep illicit drugs deprivation Nosocomial inf. Malnutrition

Alcohol/smoker Met. disturbance Anaemia

Precipitating factors
INFECTION 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 discharge. 1 in 3 survivors with delirium develop cognitive impairment. 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 impaired. 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 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.

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

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

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.

The Assessment tool!

Feature 1: Acute onset of mental status changes, or Fluctuating course.
AND

Feature 2: Inattention
AND

Feature 3: Disorganised thinking

OR

Feature 4: Altered level of consciousness

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 +

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

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.

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

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

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