Delirium in critical illness

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Delirium in critical illness
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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

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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

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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

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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. 200351(5)591

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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

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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 20012862703-2710 Ely et al CCM
  200191370-1379
• Peterson et al JAGS 2006 in press
  McNicholl JAGS 200351591-598

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Risk factors
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Precipitating factors

• INFECTION
• Hyponatraemia
• Temperature
• Maintenance of arterial pressure
• Glucose
• Benzodiazepines
• Hypoxia, hypercarbia
• Vaquero et al. Sem in Liver Dis. 20033259-69

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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. Anesth104(1)21-26,2006Duboi
  s ICM 2001271297-1304,
• Marcantonio. JAMA, 19942721518-1522, Gadreau J
  of Clin Onc. 23(27)6712-6718

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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

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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 200127,1892-1900, Ely JAMA
  20042911753-1762, Lim SM, CCM
  2004322254-2259, Milbrandt E, CCM
  200432955-962, Jackson Neuropsychology Review
  20041487-98

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Delirium and death

• In 275 medical ITU patients
• Independent predictor 6 month mortality
• 34 with delirium v. 15 without p0.03
• 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 199928(6)551-6, Ely et al
  JAMA 20042911753-1762

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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 199928551-556

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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 200531(4)1226-1234

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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.

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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 CCM291370-1379, 2001, Ely et al
  JAMA2862703-2710, 2001

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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

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CAM-ICU

• Incorporates 4 key features from definition of
  delirium, 1 minute to do
• Change in mental status from baseline or
  fluctuating course.
• Inattention
• Disorganised thinking
• Altered level of consciousness
• Needs 1 2 with either 3 or 4.

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

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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 1999340(9)669

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ManagementPharmacological therapy

• Antipsychotics
• Haloperidol dopamine receptor
• antagonist D2, variable sedation
• side effects torsades de pointes (QTc)
• extrapyramidal.
• Newer atypicals Olanzepine, Quetiapine
• Benzodiazepines
• Deliriogenic, alcohol withdrawal.

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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

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Delirium and Negative outcomeCause-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 d
  contributing to MOF.
• Bergeron Critical Care 20059R375-381

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• www.icudelirium.co.uk
• www.icudelirium.org