delirium in critical illness. delirium an acute medical condition an acute medical condition common...
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Delirium in critical illness
Delirium
An acute medical conditionAn acute medical condition Common in UK critical care patients Common in UK critical care patients Serious adverse outcomesSerious adverse outcomes Bedside diagnosisBedside diagnosis May be first sign of a new infectionMay be first sign of a new infection Pathological not psychologicalPathological not psychological
Delirium
Disturbance of consciousnessDisturbance of consciousness Acute change in mental status Acute change in mental status Fluctuating course – worse at nightFluctuating course – worse at night Develops over short time, hours to daysDevelops over short time, hours to days Impaired attentionImpaired attention Disorganised thinkingDisorganised thinking
Delirium motoric types
Hyperactive – psychomotor agitation Hyperactive – psychomotor agitation Hypoactive – psychomotor lethargy and Hypoactive – psychomotor lethargy and
sedation, appears quiet & co-operative BUT sedation, appears quiet & co-operative BUT with inattention and disorganised thinking.with inattention and disorganised thinking.
Mixed – fluctuating hypo/hyperactive Mixed – fluctuating hypo/hyperactive symptomssymptoms
“Acute brain dysfunction”
Prevalence of up to 80% quoted in ITU Prevalence of up to 80% quoted in ITU 100 ITU surgical patients:100 ITU surgical patients:
69% with delirium69% with deliriumLonger ventilation & ITU stay – 4 daysLonger ventilation & ITU stay – 4 daysMidazolam use strongest modifiable predictorMidazolam use strongest modifiable predictor
Pandiharipande et al. 2006 SCCMPandiharipande et al. 2006 SCCM
118 ITU medical patients over 65:118 ITU medical patients over 65:31% on admission.31% on admission.70% during hospitalisation70% during hospitalisation
McNicoll J AM Geriatri Soc. 2003;51(5):591McNicoll J AM Geriatri Soc. 2003;51(5):591
PathophysiologyPathophysiology Neuroimaging – 42% ↓CBF, atrophyNeuroimaging – 42% ↓CBF, atrophy Psychoactive drugs 3-11 fold ↑RR deliriumPsychoactive drugs 3-11 fold ↑RR delirium Related to surgery – multifactorialRelated to surgery – multifactorial Biomarkers – serum anticholinergic activityBiomarkers – serum anticholinergic activity Neurotransmitters – imbalance in all Neurotransmitters – imbalance in all
monoamines, GABA, glutamate and Achmonoamines, GABA, glutamate and Ach Sepsis: blood brain barrier breakdown or Sepsis: blood brain barrier breakdown or
damage by metabolic/inflammatory damage by metabolic/inflammatory mediatorsmediators
Yokota. Psych.Clin.Neurosci 2003, Fong. J Geront A Biol Sci Med Sci 2006, Koponen J Nerv Ment Dis 1989, 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 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 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 2007Goyette Semin Resp CCM 2004, Sharshar ICM 2007
Delirium is often invisible
The vast majority of delirium in ICU is either The vast majority of delirium in ICU is either hypoactive “quiet” subtype (35%) or mixed (64%)hypoactive “quiet” subtype (35%) or mixed (64%)
Very little (1%) is the pure hyperactive subtype.Very little (1%) is the pure hyperactive subtype. Older age is a strong predictor of hypoactive deliriumOlder age is a strong predictor of hypoactive delirium Hypoactive delirium has worse outcomesHypoactive delirium has worse outcomes Onset: ICU day 2 (+/- 1.7) Onset: ICU day 2 (+/- 1.7) How long: 4.2 (+/- 1.7) daysHow long: 4.2 (+/- 1.7) days Ely et al JAMA 2001;286:2703-2710 Ely et al CCM 2001;9:1370-1379Ely 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;51:591-598Peterson et al JAGS 2006 in press McNicholl JAGS 2003;51:591-598
Risk factorsHost factorsHost factors Acute illnessAcute illness Iatro/environIatro/environ
ElderlyElderly Severe sepsisSevere sepsis Sedative/analgesSedative/analges
Co-morbiditiesCo-morbidities ARDSARDS ImmobilisationImmobilisation
Pre-existing Pre-existing cognitive impaircognitive impair
MODSMODS TPNTPN
Hearing/vision Hearing/vision impairmentimpairment
Drug OD or Drug OD or illicit drugsillicit drugs
Sleep Sleep deprivationdeprivation
Neurological disNeurological dis Nosocomial inf.Nosocomial inf. MalnutritionMalnutrition
Alcohol/smokerAlcohol/smoker Met. disturbanceMet. disturbance AnaemiaAnaemia
Precipitating factors Precipitating factors
INFECTIONINFECTION HyponatraemiaHyponatraemia TemperatureTemperature Maintenance of arterial pressureMaintenance of arterial pressure GlucoseGlucose BenzodiazepinesBenzodiazepines Hypoxia, hypercarbiaHypoxia, hypercarbiaVaquero et al. Sem in Liver Dis. 2003;32:59-69Vaquero et al. Sem in Liver Dis. 2003;32:59-69
Medications cause delirium
Different drugs implicated in different studiesDifferent drugs implicated in different studies Benzodiazepines, esp. lorazepam Benzodiazepines, esp. lorazepam
?related to dose?related to dose CorticosteroidsCorticosteroids MorphineMorphine Maybe propofol and fentanylMaybe propofol and fentanyl AnticholinergicsAnticholinergicsPandharipande et al. Anesth;104(1):21-26,2006Dubois ICM 2001;27:1297-1304,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):6712-6718Marcantonio. 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 After adjusting for age, gender, race, pre-existing
comorbidity & cog impairment, ICU diagnosis and comorbidity & cog impairment, ICU diagnosis and severity of illnessseverity of illness
3 fold higher rate of death by 6 months3 fold higher rate of death by 6 months 1.6 fold increase in ICU costs.1.6 fold increase in ICU costs. Longer hospital staysLonger hospital stays Nearly 10x rate cognitive impairment on discharge.Nearly 10x rate cognitive impairment on discharge. 1 in 3 survivors with delirium develop cognitive 1 in 3 survivors with delirium develop cognitive
impairment.impairment. InstitutionalisationInstitutionalisation
Does it matter?
Increased ICU LOS 8 vs. 5 daysIncreased ICU LOS 8 vs. 5 days Increased Hosp. LOS 21 vs. 11 daysIncreased Hosp. LOS 21 vs. 11 days Increased time on vent 9 vs. 4 daysIncreased time on vent 9 vs. 4 days Higher costs $22 000 vs. $13 000Higher costs $22 000 vs. $13 000 3 fold increased risk of death3 fold increased risk of death Poss. incrd longterm cognitive impairmentPoss. incrd longterm cognitive impairment Ely ICM 2001;27,1892-1900, Ely JAMA 2004;291:1753-1762, Lim SM, CCM 2004;32:2254-2259, 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;14:87-98Milbrandt E, CCM 2004;32:955-962, Jackson Neuropsychology Review 2004;14:87-98
Delirium and death
In 275 medical ITU patients In 275 medical ITU patients Independent predictor 6 month mortality: Independent predictor 6 month mortality: 34% with delirium v. 15% without p=0.0334% with delirium v. 15% without p=0.03After adjusting for covariatesAfter adjusting for covariatesHazard ratio death: 3.2 (CI 1.4 – 7.7)Hazard ratio death: 3.2 (CI 1.4 – 7.7)203 general medical patients203 general medical patients
Adj. relative mortality risk 1.8Adj. relative mortality risk 1.8Median survival 510 days v. 1122 daysMedian survival 510 days v. 1122 days
Rockwood Age & Aging 1999;28(6):551-6, Ely et al JAMA 2004;291:1753-1762Rockwood 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 203 patients, 38 with delirium – 22 with dementia, 16 without. 32 month follow up.dementia, 16 without. 32 month follow up.
Incidence of dementia 5.6% per year without Incidence of dementia 5.6% per year without delirium, 18.1% with.delirium, 18.1% with.
Relative risk of death adjusted incr 1.8 + Relative risk of death adjusted incr 1.8 + significantly shorter median survival timesignificantly shorter median survival time
Rockwood et al, Age and aging 1999;28:551-556Rockwood et al, Age and aging 1999;28:551-556
Medical ITU patients
11 of 34 patients neuropsychologically 11 of 34 patients neuropsychologically impaired.impaired.
Generally diffuse but primarily areas of Generally diffuse but primarily areas of psychomotor speed, visual & working psychomotor speed, visual & working memory, verbal fluency and visuo-memory, verbal fluency and visuo-construction.construction.
Clinically significant depression in 36% Clinically significant depression in 36% these patients.these patients.
Jackson CCM 2005;31(4):1226-1234Jackson CCM 2005;31(4):1226-1234
Delirium and outcome
40 year old ARDS ICU survivor college graduate40 year old ARDS ICU survivor college graduate
““I have been out of hospital and trying to get on with I have been out of hospital and trying to get on with my life for the past 2 years. I have trouble with my life for the past 2 years. I have trouble with people’s names that I have worked with for years. people’s names that I have worked with for years. I can’t remember where I put things at home. I I can’t remember where I put things at home. I can’t help my children with their homework can’t help my children with their homework because I can’t remember how to do simple because I can’t remember how to do simple multiplication problems.”multiplication problems.”
Neurological monitoring
Level of sedation.Level of sedation.Drugs are given with specific agreed Drugs are given with specific agreed target of effect.target of effect.
Screen for deliriumScreen for deliriumConfusion assessment method for the ICUConfusion assessment method for the ICUCAM-ICU, sensitivity/specificity 95%CAM-ICU, sensitivity/specificity 95%V. high inter-rater reliabilityV. high inter-rater reliability
Ely et al CCM;29:1370-1379, 2001, Ely et al JAMA;286:2703-2710, 2001Ely et al CCM;29:1370-1379, 2001, Ely et al JAMA;286:2703-2710, 2001
Delirium screeningDelirium screening
CAM-ICU – 4 featuresCAM-ICU – 4 features
Altered mental statusAltered mental status
InattentionInattention; Indentify As in 10 letter spoken sequence; Indentify As in 10 letter spoken sequence
SAVE A HAARTSAVE A HAART
Disorganised thinkingDisorganised thinking
Altered level of consciousnessAltered level of consciousness
ICDSC – 8 itemsICDSC – 8 items
Over one shift. 4 or more = deliriumOver one shift. 4 or more = delirium
Ely JAMA 2001, Bergeron ICM 2001Ely JAMA 2001, Bergeron ICM 2001
CAM-ICU Incorporates 4 key features from Incorporates 4 key features from
definition of delirium, 1 minute to dodefinition of delirium, 1 minute to do
1.1. Change in mental status from baseline or Change in mental status from baseline or fluctuating course.fluctuating course.
2.2. InattentionInattention
3.3. Disorganised thinkingDisorganised thinking
4.4. Altered level of consciousnessAltered level of consciousness
Needs 1 & 2 with either 3 or 4.Needs 1 & 2 with either 3 or 4.
The Assessment tool!The Assessment tool!Feature 1: Acute onset of mental
status changes, or Fluctuating course.
Feature 2: Inattention
AND
AND
Feature 3: Disorganised thinking
Feature 4: Altered level of consciousness
OR
CAM-ICUSedation level at least eye-opening to voice with or without Sedation level at least eye-opening to voice with or without
eye contact.eye contact.Feature 1:Feature 1: is patient different from baseline? is patient different from baseline?Or: any fluctuations in mental status 24/12?Or: any fluctuations in mental status 24/12?Feature 2: Feature 2: looking for inattention – ASE letters, if unclear looking for inattention – ASE letters, if unclear
status – ASE pictures using hand squeeze.status – ASE pictures using hand squeeze.If both positive:If both positive:Feature 3: Feature 3: Disorganised thinking, a) 4 questions – 2 or more Disorganised thinking, a) 4 questions – 2 or more
incorrect responses is positive. b) Holding up fingers.incorrect responses is positive. b) Holding up fingers.Feature 4: Feature 4: Altered conscious level i.e. drowsy + Altered conscious level i.e. drowsy +
Management: treat cause(s) & reduce risks
Treat underlying infection and CCFTreat underlying infection and CCF Correct metabolic disturbance & hypoxiaCorrect metabolic disturbance & hypoxia Frequent reorientation of patientFrequent reorientation of patient Goal directed sedation/analgesia &/or daily Goal directed sedation/analgesia &/or daily
wakeup.wakeup. Stop ventilator each day to test readinessStop ventilator each day to test readiness Early mobilisationEarly mobilisation Attention to optimising sleep patterns Attention to optimising sleep patterns Inouye. NEJM 1999;340(9):669Inouye. NEJM 1999;340(9):669
ManagementManagementPharmacological therapyPharmacological therapy
Antipsychotics:Antipsychotics:Haloperidol: dopamine receptorHaloperidol: dopamine receptor
antagonist Dantagonist D2, 2, variable sedation variable sedation
side effects: torsades de pointes (QTc)side effects: torsades de pointes (QTc)extrapyramidal.extrapyramidal.Newer atypicals: Olanzepine, QuetiapineNewer atypicals: Olanzepine, QuetiapineBenzodiazepines:Benzodiazepines:Deliriogenic, alcohol withdrawal.Deliriogenic, alcohol withdrawal.
Haloperidol
1950 shortly after chlorpromazine1950 shortly after chlorpromazine D2 blockade mesolimbic pathwaysD2 blockade mesolimbic pathways Blockade in nigrostriatal pathway – EPSBlockade in nigrostriatal pathway – EPS Fewer vasomotor, cardiac central effectsFewer vasomotor, cardiac central effects 60% bioavailability60% bioavailability Metabolised by oxidative dealkylationMetabolised by oxidative dealkylation Various dose schedulesVarious dose schedules 2.5mgs to 5mgs starting dose2.5mgs to 5mgs starting dose
Delirium and Negative outcomeCause-and-effect? Systemic infections & injury Systemic infections & injury ►► brain brain
dysfunction generation of CNS dysfunction generation of CNS inflammatory response inflammatory response ►►Production of Production of cytokines, cell infiltration & tissue damage.cytokines, cell infiltration & tissue damage.
CNS immune activation accompanied by CNS immune activation accompanied by peripheral production of TNF, interleukin 1 peripheral production of TNF, interleukin 1 & interferon & interferon δ contributing to MOF.δ contributing to MOF.
Bergeron Critical Care 2005;9:R375-381Bergeron Critical Care 2005;9:R375-381
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